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A COMPLETE AND UPDATED REVIEW ON VARIOUS TYPES OF DRUG DELIVERY SYSTEMS

July 2020
International Journal of Applied Pharmaceutics 12(4):1 - 16

July 2020
12(4):1 - 16

DOI:10.22159/ijap.2020v12i4.37508

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CC BY 4.0

Authors:

Rajeev Garg

Guru Nanak College Of Pharmacy

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The World of medicine has gained considerable interest in the research area all over the World. Scientists constantly work on the three parameters 'Quality, Safety, Efficacy' of a pharmaceutical ingredient. Refine these parameters; they are continually developing different dosage forms. These unique types of dosage forms help to provide improved bioavailability and efficacy of a pharmaceutical ingredient. The role of dosage form is to improve the availability of the medicine to treat the symptoms and disease. This article focus on the different types of dosage forms, their advantages and some important facts related to that dosage forms.

Different types of routes for parenteral drug delivery

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A COMPLETE AND UPDATED REVIEW ON VARIOUS TYPES OF DRUG DELIVERY SYSTEMS

Review Article

RAJEEV GARG1, SHARANPREET KAUR1, RITIKA1, SHEHNAZ KHATOON1, NAINA1, HITESH VERMA1,2

1Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial College of Pharmacy, Bela, Rupnagar, Punjab, India 140111, 2

Email: sharankashyap1@gmail.com

Overseas R&D Centre,

Overseas Healthcare Pvt. Ltd., Phillaur, Punjab, India

Received: 18 Mar 2020, Revised and Accepted: 24 Apr 2020

ABSTRACT

The World of medicine has gained considerable interest in the research area all over the World. Scientists constantly work on the three parameters

‘Quality, Safety, Efficacy’ of a pharmaceutical ingredient. Refine these parameters; they are continually developing different dosage forms. These

unique types of dosage forms help to provide improved bioavailability and efficacy of a pharmaceutical ingredient. The role of dosage form is to

improve the availability of the medicine to treat the symptoms and disease. This article focus on the different types of dosage forms, their

advantages and some important facts related to that dosage forms.

Keywords: Different types of tablets, Vaccines, Microsponges, Suppositories, Capsules, Ointments, Gels, Biphasic dosage form, Targeted drug

delivery systems, Osmotic drug delivery systems, Controlled drug delivery systems

DOI: http://dx.doi.org/10.22 159/ijap.2020v12i4.37508. Journal homepag e: https://innovareacademics.in /journals/index.php/ijap

INTRODUCTION

The world of medicine and medical science deals with the

prevention, cure and treatment of any ailment which alters the

functions of the human body. The word ‘Medicine’ is derived from

the Latin word ‘Medicus’ which referred to ‘a Physician’. Medicine is

an agent or a substance which is taken by a person by any route to

treat the abnormal functions of the body.

China, Babylon, Egypt and India introduced the medical science to

the world. Indians contributed to the different type of treatments,

diagnosis and medical ethics in the world of medical science. The

first medical school was opened in Southern Italy in the 9th century.

Then till the 20th

From 5000 y, Indians used Ayurvedic system of medicine and

medical sciences. Plants, soil and clay were used to treat the

illness. Medicine was called as ‘Aushadhi’ which can be plant

part, soil or mixtures of some liquids which cure the disease or

any infection. Ayurveda also tells about different dosage forms

which are prepared by Vaidya (a physician) by applying some

scientific knowledge. Then Vaidya mixed the ingredients derived

from various sources by grinding, percolating or using other

methods, prepared a dosage form which can be easily taken by

patients.

century, many Universities were founded in the

countries like Italy, France and England. This field progressed very

rapidly after this century.

Some dosage forms in the form of liquids like Kasaya, Arka, Sneha,

Hima and Mantha; semi solid dosage forms like Kalka, Avaleha,

Lepa, Malahara and Upanaha; solid dosage forms like Churna,

Khanda Vati Lavana and Guggulu were formulated according to

Ayurveda. In today’s World these systems are revolutionized to

different new dosage forms from macro systems (tablets,

capsules) to micro systems (microemulsion, microparticles) and

then to nano systems (liposomes, nanogels) [1]. Different types of

drug delivery systems was used as search criterion to write this

review. Literature survey was conducted over a number of years

1980-2020 to update and comprehensively review. The sources

were papers from journals that are recognized world-wide. The

keywords used as filters were-aerosols, aptamers, antisense

therapeutics, osmotic systems, pH-activated systems, micro and

nano drug delivery systems.

Further more detailed form of these modern dosage forms including

their general introduction, positive expressions is explained.

Tablets

Tablets are prepared by compressing the active pharmaceutical

ingredients with or without additives. These are intended to be used

as unit dosage forms. Tablets can be round, convex, rectangular, oval

etc. having different sizes depending on the route of administration.

Excipients such as diluents, binders, glidants, lubricants,

disintegrants, sweeteners, flavours and granulating agents are used

to formulate tablets. When the active ingredients are intended to

protect from any type of environment in vivo/in vitro coating is done

on the surface. The tablets are the most stable system than any other

dosage forms. The release of active ingredients from the tablets can

be varied by using different type of coatings and polymers [2, 3].

Compressed tablets

Compressed tablets are uncoated tablets made by compressing the

drug and excipients as a single layer or multi-layer tablets. These are

made by direct compression technique. Since no coating is applied

on these tablets, the release of the drug will be immediately [2, 3].

Sugar coated tablets

When compressed tablets are coated with a layer of sugar is called

as sugar coated tablets. The purpose of the coating is to mask the

taste of bitter drug. By varying the thickness of the layer on can also

control the release of drug from the dosage form. Sugar coated

tablets have some features like stability of drugs and ease of

administration when compared with film coated tablets. These

tablets have a graceful look and act as a barrier for environmental

changes such as oxidation and hydrolysis. The use of sugar coating is

limited these days due to its size and weight [2-4].

Film coated tablets

When compressed tablets are coated by using a thin layer of

polymers like cellulose derivatives and control the release of drug

from the tablet. It also has an elegant appearance like sugar coated

tablets. It is more stable than sugar coated film and is less bulky and

manufacturing time is less. The coating can be designed according to

the environment in which the drug is to be released [5, 6].

Enteric coated tablets

These types of tablets are coated with polymers like hydroxyl propyl

methyl cellulose (HPMC), cellulose acetate phthalate, Eudragit L-100,

Eudragit S-100 etc. These polymers protect the tablet from gastric

environment and allow the release of the drug in the intestine. Drugs

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Int J App Pharm, Vol 12, Issue 4, 2020, 1-16

that are prone to gastric acid are coated with enteric coated polymers.

Enteric coated polymers also delay the release of the drug [2, 7].

Mouth dissolving tablets

These are uncoated tablets that release the drug in the mouth when

placed. These tablets disintegrate rapidly to release the drug in the

mouth cavity before swallowing. It disintegrates into small granules

and forms gel like structure from which the drug is released. The

disintegration time is from seconds to some minutes [2, 8].

Chewable tablets

These are intended to release the drug in the mouth or in the buccal

cavity by chewing the tablets. These are used for the drugs that have

large dose and size. Chewable tablets are useful for the children and

for those who have difficulty in swallowing. To mask the taste of

drugs, sweeteners and flavours are added. This also improves the

patient compliance [2, 9].

Tablet triturates

When active ingredients are mixed with powdered sucrose or

lactose and then moistened, moulded into different shapes like

cylindrical or compressed discs are known as tablet triturates. These

are meant to be dissolved immediately. It must disintegrate rapidly

therefore compression force should be used to lesser extent [2].

Hypodermic tablets

The tablets that are meant to be dissolved in distilled water to be

injected as a solution by the parenteral route. These tablets are

made by soluble ingredients. Sterility is the major problem with

these types of tablets. Care should be taken to maintain its sterility

while using these tablets [2].

Gelatin coated tablets

These types of tablets are coated with gelatin to protect it from

environmental hazards like photosensitivity. Coloured gelatin is

used to coat the tablet. Gelatin tablets are easy to swallow and ideal

for double-blind clinical trials and the drugs that cause irritation to

the mucosal lining can be formulated as gelatin coated tablets.

Gelatin coating is better than sugar or film coating [2].

Immediate release tablets

As the name indicates, these tablets release the drug rapidly by

disintegrating immediately and are formulated without any rate

controlling coating on them. Chewable tablets, effervescent tablets,

sublingual tablets and buccal tablets are mostly used immediate

release tablets for administration of drugs [2, 10].

Extended release tablets

Controlled release, delayed release and prolonged release tablets–all

are categorized under extended release tablets. These are designed

to prolong the release of active ingredients in vivo at a

predetermined rate. The release of the drug depends upon the

physiological conditions of the body due to different type of coating

and target to be treated. Sometimes, the drug releases in a pulsatile

manner in order to give repeat action [11].

Vaginal tablets/Inserts

Vaginal tablets or inserts are uncoated, ovoid, pear shaped tablets

employed vaginal infections. These tablets can provide local or

systemic effects by dissolving slowly and releasing the drug [2].

Implant tablets

When the tablet is inserted directly into the skin (subcutaneously)

with the help of surgery are known as implant tablets. They slowly

release the drug over a long period of time. They have replaced the

traditional system of medication. These preparations are sterilized

and mostly made by the fusion method. Hormones like testosterone

and contraceptives are administered by using these implants. They

are made by using rate controlling polymers and additives.

Formulations like pallets, resorbable microparticles, polymer

implants, in–situ gel forming implants, metal or plastic implants and

drug eluting stents are available in the market [2].

Lozenges

The term "Lozenge" derives from the French word "Losenge," which

means a structure in the shape of a diamond with four equal sides. In

pharmacy since the 20th century, lozenges and pastilles have been

produced and are still under commercial production. Lozenges are

solid preparations intended for mouth or pharynx dissolution. These

may contain one or more drugs in a flavoured and sweetened base and

are intended to treat local pain, mouth or pharynx infection and may

also be used to absorb systemic drugs. We can deliver medication to

the oral cavity or mucosal surface multi-directionally. Lozenges are

placed in the oral cavity in a better innovative dosage form.

Historically, lozenges have been used to relieve minor sore throat pain

and irritation and have been widely used to provide topical

anaesthetics and antibacterial treatment. Currently lozenges include

the following different categories of drugs: analgesics, anaesthetics,

antimicrobials, antiseptics, astringent antitussives, decongestants,

demulcents, and other groups and medication combinations. These

can be prepared by moulding (Pastilles) and compression tablets

(Troches) depending on the type of lozenge [12-15].

Advantages

1. It can be given to patients who are having trouble swallowing.

2. Services for geriatric and pediatric use.

3. The length of the drug in the oral cavity is prolonged to achieve a

specific effect.

4. Easy to plan, with minimal equipment and time required.

5. Do not require administration of the form of water intake.

Systemic drug absorption by the buccal cavity may be possible.

6. Sweeteners and flavors used in the formulation that mask the

taste of the drugs.

7. Like parenterals, this procedure is non-invasive.

8. While bioavailability can increase, it may decrease the dosing

frequency. It can reduce the pain of the stomach.

9. It can boost the start of operation.

10. It can bypass metabolism for the first time.

11. Increased treatment of patients.

Classification of lozenges

According to action site

(a) Local impact example-Decongestants, antiseptics.

(B) Systemic Effect example-Nicotine, vitamins.

According to texture and composition-

(a) Chewy or caramel-based medicinal lozenges

(b) Compressed lozenges

(d) Hard lozenges

Chewy or caramel-based medicinal lozenges

These are dosage forms in which medicinal products are

incorporated in a caramel base that is chewed rather than dissolved

in the mouth. The chewable lozenge, or "gummy-type" candy

lozenge, is one of the most common lozenges for paediatric use.

These gelatin-based pastilles were prepared by pouring the melt

into moulds or uniform thickness onto a sheet [16, 17].

Compressed lozenges

The active ingredient may be prepared by compression when it is

heat-sensitive. The process of granulation is identical to that used

for any tablet compressed. These tablets differ from conventional

tablets in terms of

• Organoleptic property,

•

• Profiles with gradual dissolution.

Options that do not disintegrate

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The lozenge is made using heavy compression equipment to give a

tablet that is harder than usual so gradually dissolving in the mouth

is better for the troche. Commercially, tablet compression

preparation of lozenges is less essential.

Soft lozenges

Due to the ease of extemporaneous preparation and applicability to

a wide variety of drugs, soft lozenges have become popular. The

bases are usually a mixture of various polyethylene glycols, acacia or

similar materials. One type of these soft lozenges is the pastille,

described as a soft, typically transparent lozenge variety consisting

of a gelatin, glycerogelatin or acacia medication: sucrose base. Soft

lozenges are similar to a drug that makes the "confection" comeback.

Confections are classified as soft masses with heavy saccharinity

medicinal agents [13].

Hard candy lozenges

Hard candy lozenges are mixtures of sugar and other carbohydrates

in an amorphous (noncrystalline) or glassy state. They can also

regards as solid syrups of sugar. The moisture content and weight of

hard candy lozenge should be between, 0.5 to 1.5 % and 1.5-4.5 g

respectively. We should be dissolved or degraded gradually and

evenly for 5-10 min and should not disintegrate. Generally the

temperature requirements for their preparation are high, so heat-

labile materials cannot be integrated into them. Via heating and

congealing process these pastilles was prepared.

Suppositories

Suppositories are semi-solid dosage system most often placed into the

rectum, vagina, or nasal cavity body to supply medications to the

systemic circulation or local tissues. The drug is included into the

suppository base and is prepared to either melt or dissolve in the body

cavity fluid to release the drug. They are accessible in diverse weight,

sizes and shapes. They use to produce local, systemic and mechanical

action. These can be easily given to children, old people and

unconscious patients who are unable to easily swallow the medication.

These are incorporated into the body cavity to create the local effect of

the drug in the base. These are inserted into the rectum to work

directly and efficiently on the rectum and to facilitate bowel

evacuation. These are unit dosage system. These are effective methods

of administering drugs that irritate the gastrointestinal tract, cause

vomiting and disrupt the acidic pH of the stomach juice.

Types of suppositories

Rectal suppositories

For their systemic effect, these are intended to be introduced into

the rectum. These types of suppositories are usually made from

Theobroma oil and are available in diverse sizes to meet the needs of

infants, adults and children. Weight of rectal suppository is usually

1-2 g. They are either torpedo or cone shaped.

Vaginal suppositories

These are intended to be introduced into vaginal. Also known as

pessaries, these suppositories are larger than rectal suppositories.

Vaginal suppositories may be conical, rod shaped, or wedge-shaped

and usually 4-8 of weight is available. Vaginal tablets and vaginal

capsules that have replaced vaginal suppositories are also available

nowadays.

Nasal suppositories

These are meant for nasal cavity penetration and are also known as

nasal bougies. These are similar to the suppositories of urethra. These

are small and cylindrical in shape and are always made with a base of

glycero-gelatin. They are about 9-10 cm long and about 1.0 g in weight.

Urethral suppositories

These are meant for urethra implementation and are also referred to

as urethral bougies. To allow insertion, these are small, long and

cylindrical shapes at one end. Their weight ranges between 2-4 g.

These suppositories are used very seldom.

Ear cones

These are intended for ear insertion and are also known as

aurinaria. These are rarely used today. These suppositories are

about 1 g in shape and weight, thin, long, and cylindrical. Usually

theobroma oil is used to prepare the ear cones [18, 19].

Pellets

Pelletized dosage forms date back to the 1950s, when the first

product was introduced to the market. In 1949, research scientists

of SmithKline and French advanced tiny drug pellets which are filled

into capsules. Since then, these dosage forms have gained

considerable popularity because of their distinct benefits inclusive of

enhancement of drug dissolution. Pellets are small, free flowing,

systematically produced, spherical or semi spherical solid units,

geometrically defined agglomerates of about size ranging from 0.2

mm to 2.0 mm, obtained from numerous starting materials of fine

powders or granules of bulk drugs and excipients using different

pelletization techniques. Pellets supposed for oral use are

administered in the form of hard gelatin capsules or disintegrating

tablets which rapidly liberate their contents inside the stomach and

gets distributed all through the gastrointestinal tract without loss of

the depot impact as the sub-unit acts as self-contained depots.

Pellets offer greater flexibility within the design and development of

an active element into oral dosage forms like tablets, capsules and

suspension with significant therapeutic benefits over single units. As

subunits various kinds of particles with described less-porous

surface, spherical shape, and low surface area to volume ratio are

suitable for flexible and uniform drug polymer coating [20].

Capsules

The term ‘Capsule’ derived from Latin word Capsula [21]. The

invention of the gelatin capsule is generally credited to Moths and

Dublanc, two Frenchmen. Their patents, issued in March and

December 1834, covered a method of producing single-piece, olive-

shaped, gelatin capsules that were closed after a drop of condensed,

moist gelatin solution had been filled. In 1865, the two-piece

telescopic tube, invented by London's jam Murdock, was patented in

England [22]. In pharmacy, capsule term has been used to define a

glass ampoule and also as a name of a protective cap over the

stopper of a bottle of medicine. Recently, capsules have been mainly

used to identify types of solid dosage form, consisting of a container

which is filled with medicinal material. Capsules are divided in two

classes,’ soft capsule’ (one piece) and ‘hard capsule’ (two piece)

according to the presence of glycerol or another plasticizer that

make it soft and elastic [23]. Benefits of capsules such as drugs with

an unpleasant smell and taste can be conveniently administered;

Less supplements are needed compared to tablets; they are

inexpensive; once they come into contact with water, they are

slippery and quick to swallow with water; the shells are

physiologically inert and digested in the GIT easily and quickly; the

shells can be opacified or coloured to provide light protection [24].

Ocular drug delivery system

Ocular drug delivery systems are used for the treatment of eye

infection/diseases by installing directly into the eye (topical,

intraocular and periocular). Ocular preparations are sterile and free

from particles and pyrogens. Eye drops, eye ointments, eye lotions

etc. are the examples of ocular drug delivery systems.

Eye drops are meant to be installed into the conjunctiva sac and can

be hydrophilic and/or lipophilic preparations. These are sterile

preparations which are free from any particulate matter. Drugs like

antiseptics, anaesthetics, mydriatics and meiotic can be incorporated

into eye drops.

Eye Ointments are semi-solid aseptic preparations. They are

composed of mineral oil and soft paraffin with drugs and are

anhydrous primarily. Due to its semi-solid nature, it stays for

prolong time in the eye and provide better bioavailability. These are

available for single use also to avoid contamination.

Eye Lotions are concentrated preparations used for washing of

eyes. It can be diluted with warm water. These preparations must be

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isotonic, sterile and free from grittiness. The pH of the solution must

be equal to lachrymal fluid and should be non-irritant [25, 26].

Aerosols

Pharmaceutical aerosols are the systems in which propellants are

used to disperse fine drug particles into it under pressure. So

aerosols are defined as pressurised systems containing therapeutic

ingredients which deliver the drug in mist or gaseous form upon

pressing the outlet valve. Sterilization can be maintained throughout

its shelf life. By using metered dose valve, potent drugs can be

administered with safety and accuracy. The drugs are protected

from environmental factors like oxidation, hydrolysis and light [27].

Buccal drug delivery system

Buccal drug delivery system is a system in which the drug is

delivered through the buccal mucosa [28]. Buccal mucosa lines the

inner area of cheeks [29, 30]. Advantages of buccal drug delivery

system such as it avoids first-pass metabolism and enzyme

metabolism; as compared to sub-lingual, buccal drug delivery

system have large surface area; in case of toxicity it can be easily

removed and easy to administer; it plays important role in that case

in which patients are unconscious and comatose [31, 32].

Gastro-retentive drug delivery system

Gastro-retentive drug delivery systems can stay in the gastric area for

several hours, substantially increasing drug residence and prolonging

gastric retention; enhancing bioavailability, decreasing drug waste and

improving solubility. Gastro retention provides better availability and

local drug delivery to stomach and intestine [33]. Categories of gastro-

retentive drug delivery system are effervescent system, non-

effervescent system, hollow microspheres/microballons and

microporous compartment system [34].

These drug delivery systems offer benefits such as drug delivery in

small intestine area with narrow absorption window. Floating

systems are beneficial for stomach absorbed drugs e. g. antacid salt.

Specific site intake from the upper part of the gastrointestinal time

may lead to the development of drugs with poor bioavailability as a

floating drug delivery system to maximize their absorption. Due to

the long term release impact, floatability and standardized release of

the drug through a multi-practice scheme preventing gastric

irritation. These systems provide better therapeutic effect of short

lived medicinal products [35].

Nasal drug delivery system

Nasal drug administration has been used as a different route for the

systemic availability of drugs constrained to intravenous

administration. This is due to the large surface area, porous

endothelial membrane, high total blood flow, metabolism avoidance

and ready accessibility. Upon intranasal administration, drugs are

quickly removed from the nasal cavity, resulting in rapid systemic

drug absorption [36, 37]. For the following reasons, nasal delivery is

considered a promising technique: The nose has a large surface area

accessible for drug absorption due to the penetration of the epithelial

surface by multiple microvilli, the subepithelial layer is highly

vascularized, the venous blood from the nose passes directly into the

systemic circulation and thus avoids the loss of the drug through first-

pass metabolism in the liver, allowing lower doses, quicker therapeutic

bladder attainment, less side effects, high total blood flow per cm3

Pulmonary drug delivery system

easily accessible porous endothelial basement membrane, and drug

delivery directly to the brain via olfactory nerves [38-40]. The

respiratory mucosa is the perfect area for the absorption of drugs [41].

Drug deliveries to the respiratory tract, via inhalation, to treat the

bronchial diseases are referred as pulmonary drug delivery systems.

This system is very beneficial in the treatment of asthma, chronic

obstructive broncho-pneumopathy. Therapeutic action is fast due to

the direct administration on the site of action. These systems also

bypass the first pass metabolism. Dose is less and ease of

administration provides better patient compliance. Pressurized

metered dose inhalers (pMDI) or dry powder inhalers (DPI) are the

examples of pulmonary drug delivery systems [42].

Hepatic drug delivery system

It is the type of targeted drug delivery systems. The drug is

administered via any type of novel drug delivery systems such as

liposomes, niosomes, microparticles etc. When the drug reaches at

the site if action i.e. liver via blood circulation, the drug is actively

taken by hepatic cells and cure the hepatic diseases. The delivery

systems must be made in such a way that they only release their

drug on target site and should be protected from harsh environment

of other organs. The drug must accumulate within the liver cells to

achieve the desired therapeutic concentration. Probucol liposomes,

Mannosylated superoxide dismutase (SOD), Ursodeoxycholic acid

(UA) modified protein-lipid nanocomplex, Super paramagnetic iron

oxide (SPIO) nanoparticles are some drugs used to treat hepatic

disorders [43].

Monoclonal antibodies

Monoclonal antibodies are defined as the single clone molecules of a

particular parent cell which are produced by hybridoma cells or cell

line and is identical i.e. identical in structure, idiotype, affinity, and

specificity for specific epitope. Monoclonal antibodies can be used

alone or in conjugation with drugs, toxins, cytokines or isotopes. In

the past years, the main source of the antibodies was human or

animal blood but it had a basic issue i.e. it contains polyclonal

antibodies meaning it can bind to several epitopes and show many

type of immune reactions. It has advantages like one can get

unlimited supply of single type of antibodies having specific activity

to unlimited period of time [44, 45].

Aptamers

Aptamers are defined as oligonucleotides that are derived by the

process Systematic Evolution of Ligands by Exponential Enrichment

(SELEX). They are categorised as DNA or RNA aptamers having short

strands of oligonucleotides and peptides aptamers having one or

more peptide chains. Aptamers inhibits the activity of cancer cells

and bacteria. Aptamers control the release of bio molecule

therapeutics. But aptamers form weak bonds with the protein

binding sites which are too weak to show its activity. They also help

to activate the Polymerase Chain Reaction (PCR) enzymes which

initiate the initial phases of Polymerase Chain Reaction [46, 47].

Antisense therapeutics

These are defined as short length single stranded DNA or RNA

having base sequence complementary to particular gene or its

mRNA. Antisense oligonucleotides block the activity of ribosomal

machinery or activate the endogenous RNAase that break the mRNA

at duplex site by inhibiting the expression of unwanted cell protein

by recognizing Watson–Crick complementary base and hybridize it

to the target mRNA. The example of phosphodiester oligonucleotides

is phosphorothioate oligodeoxynucleotides (PS-oligonucleotides)

containing a sulphur instead of oxygen in one of the non-bridging

phosphate. Due to this it inhibit the rapid degradation by nucleases.

These have many properties like binding affinity to the target

(mRNA), cellular uptake, hydrophilic and the ability to activate

RNase H, which is required for antisense activity [48, 49].

Sedds, Smedds, Sndds

These systems are formed by mixing surfactants, co-surfactants, and

drugs and made isotropic mixtures. When this mixture comes in

contact with water it forms microemulsion with fine droplets in the

biological system. These are better than other lipid formulations

because of use of surfactants. The formed droplet size of self-

emulsifying drug delivery system ranges between 100 to 300 nm

[51]. Self-microemulsifying drug delivery system has particle size

less than 50 nm and self-nanoemulsifying drug delivery system have

particle size in nano range [50].

Medium chain triglycerides are used to make self-microemulsifying drug

delivery system because of their better solubility and self-emulsifying

properties. Only specific type of excipients can be used to prepare self-

microemulsifying drug delivery system. Drugs that are soluble in lipid-

surfactant mixture can be incorporated in self-microemulsifying drug

delivery system. These are transparent in nature.

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Self-nanoemulsifying drug delivery systems are better due to patient

compliance and are more stable. Self-nanoemulsifying drug delivery

systems are anhydrous in nature therefore hard gelatin capsules are

made to store the dosage form and for administration also [52].

Vaccines

Vaccines are the preparations made by using biological sources to

fight against a particular disease when injected to human or animal

by the process called vaccination. Micro-organisms that resembles

the pathogen of disease are extracted and attenuated or killed by

chemical processes are used to make vaccines. Vaccines can be given

prior to the disease as prophylactic vaccines and/or can be given

when a person catches a disease as therapeutic vaccines [53].

Attenuated vaccines are those made by decreasing the activity of

virus so that it cannot cause disease itself. Examples of this type are

typhoid, yellow fever, measles, mumps, BCG (for tuberculosis) and

rubella [54, 55].

Inactivated vaccines are those made by killing the bacteria or virus

and injected into the body which stimulates the immune system to

create immunity against that particular system. Examples are polio

vaccine, hepatitis A vaccine, rabies vaccine and some influenza

vaccines [56].

Toxoid vaccines are made by using inactivated toxic substances

that are responsible for the disease/infection instead of bacteria or

virus. Examples are tetanus and diphtheria [57].

Subunit protein vaccines are made by using only protein part of the

bacteria or micro-organism or virus instead of using whole bacteria or

virus. These proteins are capable of generating immune responses.

Some subunit vaccines are subunit vaccine against Hepatitis B virus,

the virus-like particle (VLP) vaccine against human papillomavirus

(HPV), and the hemagglutinin and neuraminidase subunits of the

influenza virus [58].

Colon targeting drug delivery system

This drug delivery system is designed to treat the local infection in

the lower part of the gastrointestinal tract (GIT) and minimizing the

side effects of the drugs. This system enhances the concentration of

the drug by protecting its absorption in upper part of the

gastrointestinal tract and made it more available in the colon to treat

the disease. It provides therapeutic satisfaction to the patients in

terms of safety, efficacy, and patient compliance. The contents in the

colon stay more than 5 d so complete drug absorption can be

obtained but stability of the drug can be compromised [59].

Gene drug delivery system

The newly discovered drug delivery system is the treatment with

genes. In this therapy, no drugs are needed to treat the disease. The

infected genes are removed, modified or mutated and then again

inserted in the infected cell. This leads to the fast and complete

recovery of the disease. It is beneficial to treat the genetic problems,

cancers and certain viral diseases. The gene delivery systems

comprises the three substances such as a gene expression system

that contain plasmid (that controls the function of a gene within the

targeting cell), a gene (to encodes a specific therapeutic protein),

and a gene delivery system (to control the delivery of the gene

expression plasmid) to the target gene within the body [60].

Magnetic drug delivery system

This drug delivery systems based on the nanoparticles with iron

oxide as a vehicle for delivery of drugs. Single molecule magnets are

used to transfer the toxic drug to the target site without

incorporating the iron oxide in that site. The main problem with this

drug delivery system is the excess concentration of iron oxide which

leads to adverse effects. But this method is beneficial in cancer

treatment by formulating “anticancer nanomagnet” [61].

Brain drug delivery system

When the drug deliveries are designed to cross the different brain

barriers are called as brain drug delivery systems. Highly lipophilic

drugs can cross blood brain barriers easily and target the brain

tumours and other infections in the brain. But due to the clearance

of the drugs rapidly from the brain cannot maintain the therapeutic

concentration of the drug. Barriers are the main problem for the

delivery of the drugs to the brain. There are many micro and nano

drug delivery systems that facilitate the delivery of hydrophilic and

lipophilic drugs across the barriers [62].

Mucoadhesive drug delivery system

Mucoadhesion is generally defined as the adhesion between two

materials, of which at least one is a mucosal surface. Mucoadhesive

dosage systems may well designed to enable prolonged retention at

the site of application, providing a controlled rate of drug release for

better therapeutic outcome. The application of dosage forms to

mucosal surfaces may be beneficial to drug molecules that are not

appropriate for the oral route, such as those suffering from acid

degradation or severe first-pass metabolism. Topical and local systems

based on Mucoadhesive have shown increased bioavailability.

Mucoadhesive drug delivery results in fast absorption and strong

bioavailability due to its large surface area and high blood flow. Drug

delivery across the mucosa bypasses the first-pass hepatic metabolism

and prevents gastrointestinal enzymes from degrading. Thus the

mechanism of delivery of mucosal drugs could be of use in delivering a

growing number of high-molecular-weight responsive molecules such

as peptides and oligonucleotides. Mucoadhesive drug delivery system

plays an important role in controlled drug delivery system [63, 64].

Benefits of Mucoadhesive drug delivery system such as;

• Targeting drug delivery system;

• High flux of drugs in the absorbing tissue

• Good accessibility

• Painless administration

• Avoid first pass metabolism

• Low enzymatic activity

Bioactive drug delivery system

It is defined as the system in which biomolecules like protein and

peptides are delivered into the body. These systems are used to

protect the bioactive molecules from the harsh environment of the

body. Proteins and peptides (like insulin, silk molecules),

polysaccharides, lipids, minerals etc can be delivered using systems

like emulsions, encapsulation and others. Edible materials can be

incorporated into this type of system. McClements et al. studied the

delivery of bioactive compounds by emulsion based systems. They

focussed on the materials used to formulate these systems to deliver

the bioactive molecules in the body [65, 66].

Osmotic drug delivery system

When drug release is dependent upon osmotic pressure is called

osmotic drug delivery system. Osmotic pressure controls the release

of the drug from the dosage form. There is a semi permeable

membrane that controls the permeability of biological fluids. The

substance that creates pressure to push the drug layer out of the

system is called osmogent. The drug is delivered through the orifice

is made by laser drilling. This type of drug delivery system is

independent of other physiological factors. Drug release can be

expressed as zero order release kinetics. The drug release from this

type of dosage can be targeted, delayed as needed [67, 68].

Transdermal drug delivery system

Drug delivery through the skin is known as Transdermal drug

delivery systems. The drug can be transferred through the skin via

transdermal patches, inotophoresis, through microfibricated needles

and electroporation.

Transdermal patches

A transdermal patch is a drug containing sticky patch which is

applied on the skin and delivered the drug to the systemic

circulation avoiding first pass metabolism. It is a painless system to

deliver the drug to treat the problems. It improves the patient

compliance. It can be easily removable in case of adverse effects and

when treatment is required no longer. Controlled drug delivery can

be achieved through this system of medication. Drug release can be

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achieved for several days to several months. Drug release is constant

and passively therefore therapeutic concentration can be

maintained. The particle size of the drug must be less than 1000

units to be incorporated into transdermal patches and the drug must

have lipophilicity and hydrophilicity to some extent [69, 70].

Inotophoresis

It is a process of applying a few miliampere of current to the

particular part of the skin for a few milliseconds by using electrodes.

These electrodes remain in contact with the formulation and skin

and therefore allow the passage of the drug through skin and heal

the problem. The example is administration of Pilocarpine and

Lidocaine (for anaesthetic purpose).

Micrfibricated microneedles

This system has a drug reservoir and needle like projections

called microneedles which extend from the drug reservoir and

projects onto the skin. The needle like projections acts as

microneedles and transdermal patch which help to deliver the

drug through the skin.

Electroporation

Drug delivery by electroporation is assisted by using high voltage

electric pulses. These pulses dilate the epidermis cells and make pores

in the skin. Then the drug diffuse through these pores into the skin.

Microspheres

Microspheres are small spherical particles, with diameters 1 μm to

1000 μm. They are spherical free flowing particles consisting of

proteins or synthetic polymers which are biodegradable in nature.

There are two types of microspheres; microcapsules and

micromatrices, which are described as-Microcapsules are those in

which entrapped substance is particularly surrounded by distinct

capsule wall and micromatrices in which entrapped substance is

dispersed during the matrix. Microspheres are every so often

referred to as microparticles. Microspheres can be manufactured

from various natural and synthetic materials. Microsphere plays a

vital role to improve bioavailability of conventional drugs and

minimizing side effects [71].

Advantages of microspheres

• Particle size reduction for enhancing solubility of the poorly

soluble drug.

• Decrease dose and toxicity.

• Better drug utilization will improve the bioavailability and

reduce the incidence or intensity of adverse effects

• Provide constant and prolonged therapeutic effect.

• Provide constant drug concentration in blood thereby increasing

patient compliance.

Microcapsules

Microencapsulation is the method of enclosing a substance

inside a miniat ure known as the capsule. Microcapsule is a small

sphere with a uniform wall around it. The material inside the

microcapsule is referred to as the core/inner phase, whereas the

wall is every so often called a shell/coating. The microcapsule

size ranges from 1 µ-7 mm. All the three states i.e. solid, liquid

and gas may also be encapsulated which may additionally have

an effect on the size and shape of capsules. If the solid or

crystalline material is used as the core, the resultant capsule can

also be irregularly shaped. If the core fabric is liquid, simple

spherical capsules containing a single droplet of encapsulate

may additionally be formed [72].

Advantages of microcapsule

 Microcapsule used for sustained or prolonged release.

 It is also used for masking taste and odour of many drugs to

improve patient compliance.

 Vaporization of many volatile drugs e. g. methyl salicylate and

peppermint oil can be prevented by microencapsulation.

 It can reduce toxicity and GI irritation including ferrous sulphate

and KCl.

 It can be used for converting liquid drugs in a free flowing

powder.

Microsponges

Won developed microsponge technology in 1987 andamp; filled

original patent for the same and it is assigned to polymer system.

Their organization developed with versions a number of

products for pharmaceutical and cosmetic use. Microsponges

consist of polymeric drug delivery system porous microspheres.

They are sponge like structure consisting of a myriad of

interconnecting voids within a non-collapsible structure with a

large porous surface and spherical in shape. Microsponges are

notably stable with less side effects and having ability of

modifying drug release. The microsponges are spherical in

nature and having particle size ranging from 5-150μm.

Microsponges are the cross-linked, porous, polymeric

microspheres which accumulate the flexibility to entrap a variety

of active ingredients. They are in most cases used for topical and

oral administration with altering release rate. The microsponges

i.e. microsponge drug delivery system (MDDS) consist of size 5-

150 μm in diameter; with a ordinary 25 μm sphere can up to

250000 pores and an interior structure of pore equal to 10 ft. in

size which provides a total pore volume of 1 ml/gm. This type of

system exhibits large reservoir within microspongic structure,

which can be loaded with the identical weight of active

ingredient [73].

Advantages of microsponges

 Microsponges can prevent accretion of active ingredient in the

epidermis and dermis.

 Microsponges can reduce irritation of effective drug by

maintaining their effectiveness.

 Microsponges drug delivery system increases residential time

of a drug on skin surface or in epidermis.

 Microsponges has stable over range of pH 1 to 11, temperature

up to 120 °C.

 Microsponges well-matched with most vehicles and ingredients.

 Microsponges can improve product elegance.

 Microsponges can improve bioavailability of the drugs.

 Microsponges have superior formulation flexibility.

Microemulsions

Microemulsions are clear, stable, isotropic liquid mixtures of oil,

water and surfactant, frequently in mixture with a co-surfactant.

The aqueous phase may also contain salt(s) and/or other

ingredients, and the "oil" may also truly be a complex mixture of

exclusive hydrocarbons and olefins. In contrast to regular

emulsions, microemulsions form upon simple mixing of the

components and do not require the high shear conditions

generally used in the formation of ordinary emulsions. The two

basic types of microemulsions are direct (oil dispersed in water,

o/w) and reversed (water dispersed in oil, w/o). In ternary

systems such as microemulsions, where two immiscible phases

(water and ‘oil’) are present with a surfactant, the surfactant

molecules may also form a monolayer at the interface between the

oil and water, with the hydrophobic tails of the surfactant

molecules dissolved in the oil phase and the hydrophilic head

groups in the aqueous phase. As in the binary systems

(water/surfactant or oil/surfactant), self-assembled structures of

exclusive types can be formed, ranging, for example, from

(inverted) spherical and cylindrical micelles to lamellar phases

and bi-continuous microemulsions, which may also coexist with

predominantly oil or aqueous phases [74].

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Advantages of micremulsions

 Microemulsions are thermodynamically stable system and the

stability allows self-emulsification of the system.

 Microemulsions act as super-solvents for drug. They can

solubilize both hydrophilic and lipophilic drugs including drugs that

are relatively insoluble in both aqueous and hydrophobic solvents.

 Use of microemulsion as delivery systems can improve the

efficacy of a drug, allowing the total dose to be reduced and thus

minimizing side effects.

 The dispersed phase, lipophilic or hydrophilic (oil in-water,

O/W, or water-in-oil, W/O microemulsions) can act as a potential

reservoir of lipophilic or hydrophilic drugs, respectively. Drug

release with pseudo-zero-order kinetics can be obtained, depending

on the volume of the dispersed phase, the partition of the drug and

the transport rate of the drug.

Microneedles

Microneedles (MNs) have been studied by means of various

researchers for delivering drug through the transdermal route and

for overcoming the limitations of the conventional approaches.

Microneedle device consists of needles of micron size, which are

arranged on a small patch. Considering the issues of the hypodermic

needle and the transdermal patch, microneedle drug delivery system

was developed and is thought to be the hybrid of both. The most

important problem related with transdermal technological know-

how is that many of the drugs are not capable to cross the pores and

skin at the required rate integral for the therapeutic action.

Researchers have developed a refined technological know-how the

use of microneedles, which permit hydrophilic high molecular

weight compounds to enter into the stratum corneum.

Administration of drugs using the microneedle device allows the

drug molecules to cross the stratum corneum layer, hence allowing

more drug molecules to enter the skin. The characteristic facts of

this technology are the faster onset of action, better patient

compliance, self-administration, improved permeability and efficacy.

Large molecules can be administered. First-pass metabolism is

avoided. Decreased microbial penetration as compared with a

hypodermic needle, the microneedle punctures only the epidermis

and enhanced drug efficacy may result in dose reduction [75].

Microparticles

Microparticles are a type of drug delivery systems where the particle size

ranges from one micron (one thousandth of mm) to a few mm. This

microencapsulation technology allows protection of drug from the

environment, stabilization of sensitive drug substances, elimination of

incompatibility, or masking of unpleasant taste. Hence, they play an

important role as drug delivery systems aiming at improved

bioavailability of conventional drugs and minimizing side effects [76].

Microballoons

Microballoons are gastro retentive drug-delivery systems with non-

effervescent approach. Microballoons (Hollow microsphere) are in

strict sense, empty particles of spherical shape without core. These

microspheres are generally free flowing powders comprising of

proteins or synthetic polymers, ideally having a size less than 200

micrometer. Microballoons are considered as one of the most

beneficial buoyant systems with the special advantages of multiple

unit systems as well as better floating properties, because of central

hollow area interior the microsphere. Novel methods concerned in

their preparation include easy solvent evaporation method,

emulsion-solvent diffusion method, single emulsion technique,

double emulsion technique, phase separation coacervation

technique, polymerization technique, spray drying and spray

congealing technique and hot melt encapsulation method. The

gradual release of the drug at desired rate and higher floating

properties in most cases depends on the kind of polymer, plasticizer

and the solvents employed for the preparation. Polymers such as

polylactic acid, Eudragit R S and hydroxy propyl methyl cellulose

acetate are used in the formulation of hollow microspheres, and the

release of drug can be modulated by using optimizing polymer

concentration and the polymer-plasticizer ratio.

Advantages such as reduced dosing frequency and thereby improve

the patient compliance; better drug utilization will improve the

bioavailability and reduce the incidence or intensity of adverse

effects, and despite the first-pass pass effect because fluctuation in

plasma drug concentration is avoided, a desirable plasma drug

concentration is maintained by continuous drug release. Hollow

microspheres are used to decrease material density and Gastric

retention time is increased because of buoyancy. Site-specific drug

delivery to stomach can be achieved [77].

Microchips

Microchip drug delivery system is the most wonderful system of

delivering the drug for a great span of time without the intervention of

the patient to whom it is fixed. It consists of varied number of sockets

containing drug (generally ranging from 50-300)

which release the drug at the fixed intervals each at a time. The

microchip delivery system consists of a substrate containing more

than one reservoir capable of holding chemical substances in the solid,

liquid, or gel form. Each reservoir is capped (i.e. with a conductive

membrane) and wired with the final circuitry controlled by a

microprocessor. This central processor should be able to actively

control electrically the exact time of release and the amounts of drugs

dispersed through controlling the dissolution of the gold membrane.

The system should be reasonable to manufacture by standard micro

fabrication techniques and still be cost-effective [78].

Syrups

Syrups are concentrated solutions of sugar such as sucrose in water

or other aqueous liquid. Due to sweetness, can masks the taste of

salty and bitter tablets and therefore serve as fine tasting

automobile. Used as care for pediatric use due to their excessive

viscosity and the “smoothness” and mouth feel quality. Enhance the

flavor Due to the wide kind of flavors of syrups which include

orange, lemon, peppermint, those are broadly acceptable.

• Simple syrups: when water is used alone for making syrup.

• Medicated syrup: Syrup with some medicinal substance.

• Flavored syrup: Syrup with some aromatic or pleasantly

flavored substances and is intended to be used as a vehicle or flavor

for prescription.

Suspensions

A Pharmaceutical suspension is a coarse dispersion in which interior

segment is dispersed uniformly at some point of the external phase.

The internal phase consisting of insoluble strong particles having a

specific range of size which is maintained uniformly throughout the

suspending vehicle with aid of single or combination of suspending

agent. The external phase (suspending medium) is generally aqueous

in some instance, may also be an organic or oily liquid for non oral use.

Deflocculated suspension: In this system, solids are present as

individual particles. They also exhibit aggregation, but

comparatively at a slower rate than the flocculated particles. These

systems have a shorter shelf life, but have greater bioavailability

when compared to flocculated systems.

Flocculated suspension: In this system particles aggregate

themselves by chemical bridging. These flocs are light, fluffy

conglomerates which are held together by weak van Waals forces

of attraction. Aggregation is achieved by adding flocculating

adding flocculating agents. For instance, by the addition of more

anions on to positively charged deflocculated particles flocculation

can be achieved. This system possesses better physical stability

characteristics, because the dissolution of flocs is a prerequisite for

drug absorption [79].

Emulsions

Emulsions are two-phase system in which the dispersed phase is

also liquid. Emulsion are defined as thermodynamically unstable

systems consisting of at least two immiscible liquid phases, one of

which is dispersed as globules the other liquid phase. Large number

of emulsion is present in nature. Examples are milk, rubber latex,

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crude oil etc. Emulsion should be used when both phases, dispersed

and continuous, are liquids. In an emulsion, one liquid (the

dispersed phase) is dispersed in the other (the continuous phase).

Examples of emulsions include vinaigrettes, homogenized milk, and

some cutting fluids for metal working.

Water-in-Oil Emulsion: An emulsion is referred to as water-in-oil, if

the dispersed phase (Internal phase) is water and the continuous

phase (dispersed medium) is oil. Examples are butter, salad

dressings. w/o emulsion are generally meant for external use,

though a few examples of internal use are available.

Oil-in-Water Emulsion: An emulsion is referred to as oil-in-water, if

the dispersed phase (internal phase) is oil and the continuous phase

(dispersed medium) is an aqueous base. These types of emulsion are

meant for both internal and external use [80, 81].

Multiple emulsions

Multiple Emulsions are complex vehicle systems in which o/w and

w/o emulsions exist in a single system. Lipophilic and hydrophilic

surfactants are exploited for stabilizing multiple emulsions

Liniments

. Water-

in-oil emulsions can be stabilized by lipophilic (oil-soluble, low HLB)

surfactants, while o/w systems are stabilized by hydrophilic (water-

soluble, high HLB) surfactants. Multiple emulsions are “emulsions of

emulsions,” in wherein the drops of the dispersed phase themselves

contain smaller dispersed droplets of a miscible liquid. Every

dispersed globule in the double emulsion makes a vesicular

structure with single or multiple watery compartments divided from

the aqueous phase via an oil phase layer. In multiple emulsion

system, solute has to transverse from inner miscible phase to outer

miscible phase by the middle immiscible organic phase; it is also

known as liquid membrane system. There are two important types

of multiple emulsions: w/o/w and o/w/o double emulsions.

Multiple emulsions are mainly used in cosmetics, pharmaceuticals,

and food. Due to their fine texture, they exhibit a smooth touch upon

application. In cosmetics, they can protect an active ingredient from

degradation and release it at a controlled rate. They can act as an

internal depot and entrap compounds from the outer diluted

continuous phase into the inner space [82].

Liniment is a liquid that you rub into the skin in order to reduce pain or

relieve stiffness. Liniments can be rubbed into the skin to relieve aches

from arthritis and stiffness in muscles. A liniment is usually in the form of

a thin liquid applied to the skin. Liniment is a medicated topical

preparation for application to the skin. Sometimes called balm or heat

rubs, liniments are of a similar or greater viscositythan lotions and are

rubbed in to create friction, unlike lotions, ointments or creams,

but patches, sticks and sprays are also available [83].

Ointments

Ointments are viscous, semisolid preparations containing both

dissolved and suspended purposeful ingredients. The ointment base

needs to be heated to above its melting temperature prior to the

addition of the other ingredients. Low-shear or blending speed is

generally used when the ointment bases or completed formulation

in cold/thick. Mixing speed and shear can be elevated while the

ointment base is liquid, to uniformly disperse the practical

ingredients. Mixers used for ointments generally rent dual-motion

counter-rotating blades with side scrapers, to maintain the fabric in

constant motion and provide efficient warmness transfer from the

partitions of the mixing vessel. External powder educators may be

used to incorporate stable ingredients. All ointments consist of a

base which chiefly acts as a carrier for the medicaments. The nature

of the base also controls its performance. Hence selection of

ointment base is very important aspect of their formulation. For

scientific understanding of per-cutaneous absorption of ointment

bases it is essential to get familiar with skin structure in relation to

drug absorption. They provide means of site specific application of

drug on affected area, which avoids unnecessary non target

exposure of drug thereby avoiding side effects. They avoid first pass

metabolism of drug. This is the convenient method for unconscious

patients having difficulty in oral administration. Comparatively they

are chemically more stable and easy to handle than liquid dosage

forms. They are suitable dosage forms for bitter taste drugs [84].

Gels

Gels are described as semi rigid systems wherein the movement of

the dispersing medium is restricted through an interlacing three

dimensional networks of particles or solvated macromolecules of

the dispersed phase.

The word “gel” is derived from “gelatin” and both “gel” and “jelly”

can be drawn again to the Latin gelu for “frost” and gel are, meaning

“freeze” or “congeal”. This origin shows the important idea of a

liquid setting to a solid-like material that does not flow, however is

elastic and retains some liquid characteristics. Use of the term “gel”

as a class originated at some point of the overdue 1800s as chemists

tried to classify semisolid substances according to their

phenomenological characteristics instead of their molecular

compositions. At that time, analytical methods wished to determine

chemical structures have been lacking. In pharmaceutical

applications, water and hydro-alcoholic solution is most common

many polymer gels showcase reversibility between the gel state and

sol, which are the fluid segment containing the dispersed or

dissolved macromolecule.

However, the formation of some polymer gels is irreversible because

their chains are covalently bonded. The three dimensional network

formed in two-phase gels and jellies is formed by numerous inorganic

colloidal clay. The formation of those inorganic gels is reversible.

Ideally, the gelling agent must be inert, safe and cannot react with

other formulation constituents. The gelling agent should produce a

sensible solid-like nature at the time of storage which is easily

broken when exposed to shear forces produced by squeezing the

tube, trembling the bottle or at the time of topical application. It

should have suitable anti-microbial agent. The topical gel must not

be sticky. The ophthalmic gel must be sterile. The apparent viscosity

or gel strength increases with an increase in the effective crosslink

density of the gel. However, a rise in temperature may increase or

decrease the apparent viscosity, depending on the molecular

interactions between the polymer and solvent. They exhibit the

mechanical characteristics of the solid state. Each component is

continuous throughout the system. There is high degree of attraction

amongst the dispersed phase and water medium so the gels remain

equally uniform upon standing and doesn’t freely settle [85].

Hydrogels

Hydrogels that is polymer networks drastically swollen with water.

Hydrophilic gels which are normally referred to as hydrogels are

networks of polymer chains which might be sometimes observed as

colloidal gels wherein water is the dispersion medium. Hydrogels

are polymeric material that exhibits the capability to swell and

retain a significant fraction of water within its structure, however

will no longer dissolve in water. Hydrogels have received

considerable attention within the past 50 y, due to their first-rate

promise in a wide variety of applications.

The ability of hydrogels to absorb water arises from hydrophilic

functional groups attached to the polymeric backbone, while their

resistance to dissolution arises from cross-links between network

chains. Many materials, each naturally taking place and synthetic, fits

the definition of hydrogels. It has the highest absorption capacity

(maximum equilibrium swelling) in saline. One can get the desired rate

of absorption (preferred particle size and porosity) depending on the

application requirement. Hydrogels has highest biodegradability

without formation of toxic species following the degradation [86].

Dendrimers

The term dendrimer comes from the Greek word 'Dendron,' which

means a tree. The synonym for Dendrimer is 'Arborols,' which also

means a tree and 'Cascade molecule'. Dendrimers are repetitively

branched molecules consisting of a monomer attached centre where

a diameter in the range of 2 to 10 nm leads to a mono-disperse, tree-

like, star-like molecules. A dendron typically contains a single group

called the focal point (branching points) that can be chemically

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handled. The first dendrimers Synthesis did by divergent synthesis

approaches by Fritz Vögtle in 1978, R. G. Denkewalter at Allied

Corporation in 1981, Donald Tomalia at Dow Chemical in 1983 and

in 1985, and by George Newkome in 1985. In 1990 a convergent

synthetic approach was introduced by Jean Fréchet.

Polyamidoamines (PAMAM) were the first synthesized dendrimers.

Simultaneously, the Newkome group documented synthesis of

related macromolecules that they called “arborols” [87, 88].

Advantages

1. In the range of 1-100 nm, dendrimers particle size in nanometer

crosses the cell membrane easily.

2. Reduced clearance due to small scale through the Reticulo-

Endothelial System (RES).

3. Dendrimer is the ideal carrier for a core-protected dysfunctional

drug.

4. It is monodispersed.

5. Dendrimer increases poorly soluble drug solubility.

6. There are several functional groups on the outer surface of

dendrimers that can be used to attach vector devices to target

specific body locations [89, 90].

Types of dendrimer

1. PAMAM Dendrimer

2. PAMAMOS Dendrimer

3. P PI Dendrimer

4. Tecto Dendrimer

5. Chiral Dendrimers

6. Hybrid Dendrimers

7. Liquid Crystalline Polymers

8. Amphiphilic Dendrimers

9. Micellar Dendrimers

10. Multiple Antigen Peptide Dendrimers

11. Frechet-Type Dendrimers

12. Multilingual Dendrimers [91-94]

Nanoparticles

There has been a growing interest in the use of nanoparticles for

drug delivery applications in recent decades. Nanoparticles are

particles of colloidal size with diameters ranging from 1-1000 nm

and may contain, absorb or disperse drugs. A wide range of

nanoparticles have been produced, consisting of a variety of

materials, resulting in delivery systems that differ in their

physicochemical properties and therefore in their applications [95,

96]. To date, a number of drug delivery mechanisms, including but

not limited to liposomes, micelles, nanospheres, niosomes,

nanocapsules, solid lipid nanoparticles, microemulsions and carbon

nanotubes, have been studied. Such systems ' success is due in part

to the several advantages they provide to distribute their product

payload. The nano-sized versatility of these delivery systems allows

them to be directly delivered into the systemic circulation without

the possibility of blocking blood vessels. The size of the nanoparticle

has been shown to be a significant factor in determining the particles

in vivo fate. Researchers have shown that opsonization and

subsequent macrophage recognition and phagocytosis are strongly

correlated with particle size. Nanoparticles have the potential of

addressing and remedying some of the most significant limitations

of traditional chemotherapy, namely, its lack of specificity and

narrow window of therapeutic efficacy. Nanoparticles are colloidal

carriers with dimensions on the nano scale (10-9

Advantages

m) [97, 98].

1. Nanoparticles drug carriers have higher stability.

2. Nanoparticles have higher carrier efficiency.

3. Facility of integration of both hydrophilic and hydrophobic

substances.

4. Nanoparticles are biodegradable, non-toxic and can be stored for

longer periods.

5. Nanoparticles reduce dosage frequency and have higher dosage

frequencies.

6. Nanoparticles can also be used for controlled drug delivery.

Liposomes

Liposomes are composed of amphiphilic molecules consisting of polar as

well as non-polar components which form colloidal particles. This self-

assembly produces a spherical structure that includes the polar

components of the molecule and the non-polar components that touch

the non-polar world. The most popular liposome distinction is the

number of lipid bilayers in the colloidal form, with unilamellar liposomes

containing one lipid bilayer and multiple liposomes with multiple lipid

bilayers. Because of their amphiphilic nature, liposomes can encapsulate

polar as well as non-polar compounds for delivery (Lasic, 1998). For

many purposes, liposomes are desirable among drug delivery

applications, including their similarity to both structure and composition

of cell membranes. In addition, liposomes can easily be produced with

amphiphilic molecules that are non-toxic, non-immunogenic, normal and

biodegradable (Haley and Frenkel, 2008; Lasic, 1998). The size of a

liposome ranges from 20 nm up to several micrometers [99-101].

Advantages

1. Providing preferential passive targeting for tumor tissues.

2. Increased efficacy and therapeutic index.

3. Increased stability by encapsulation.

4. Reduction in encapsulating agent toxicity.

5. Increased pharmacokinetic effects.

6. Used as carriers for controlled and sustained drug delivery.

7. Can be converted into different sizes.

Classification of liposomes

1. Multilamellar vesicle (MLVs)-This consists of several bilayers

with a size ranging from 100 nm-20 m.

2. Small unilamellar vesicles (SUVs)-This consists of a single

lipid bilayer with a dimeter varying from 20-100 nm .

3. Large unilamellar vesicles (LUVs)-Consists of a single bilayer

with a diameter varying from 0.1-1 m.

4. Multivesicular vesicles (MVVs)-It consists of vesicles ranging

from 100 nm to 20 m in size.

Transfersomes

The name is derived from the Latin word ‘transfere’ meaning ‘to

carry across’ and the Greek word ‘soma’ for a ‘body’. Transferosomes

are a particular type of liposomes that consist of edge activator and

phosphatidylcholine [102]. They are flexible, malleable vesicles

designed to improve active agent delivery. Transferosome is a

complex aggregate that is highly adjustable, responsive to stress.

Transferosomes have a joint infrastructure of hydrophobic and

hydrophilic molecules and can therefore provide accommodation

drug molecules with extensive range of solubility [103]. Without

observable loss, transferosomes can deform and move through

narrow constriction from 6 to 11 times lower than their own

diameter [104, 105]. This high deformability gives intact vesicles a

greater penetration. Tranferosomes have a high efficiency of

trapping, which is almost 90% for lipophilic drugs. Transferosomes

protect the encapsulated medication from metabolic degradation.

These have been commonly used as a carrier for various proteins,

anti-cancer drugs, anti-fungal drugs, analgesics, anaesthetics,

corticosteroids, sex hormone, insulin, albumin, etc. with the brilliant

delivery properties of transferosomes [106, 107].

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Nanospheres

A polymeric nanosphere can be characterized as a matrix-type, solid

colloidal particle in which drugs are dissolved, trapped,

encapsulated, chemically bound or adsorbed to the polymer matrix

of the constituent [108-110]. Usually, these particles are larger than

micelles with diameters between 100 and 200 nm and can also show

substantially more polydispersion [111]. The main aims of

developing the Nanospheres as a target delivery system to monitor

the particle size and the release of pharmacologically active agents

to achieve the site specific action of the drug at the therapeutically

optimal rate and dosage regimen [112, 113].

Advantages

1. Due to their extremely small volume, nanospheres can easily

pass through the smallest capillary vessels [114,115].

2. We should prevent rapid phagocyte removal in order to prolong

the length of the bloodstream.

3. It is easy for nanospheres to penetrate cells and tissue gaps to

enter target organs, eg. Liver, spleen, liver, lymph and spinal cord.

4. It shows the property of the controlled release.

5. Site-specific targeting by adding the ligands to the sphere’s surface.

6. Each path, including oral, nasal, parenteral, etc, can be easily

administered.

7. A significant advantage of nanospheres is also the elimination of

toxicity [116].

Nanoemulsion

Nanoparticle formulation is effectively based on nanometric-scaled

emulsion, so-called nano-emulsions, the study of nanoparticle

formulation has to include knowledge of nanoemulsion formation

governing phenomena. Nano-emulsions are nanometric-sized

emulsions, typically exhibiting diameters of up to 500 nm. Nano-

emulsions are also often referred to as miniemulsions, fine-

dispersed emulsions, submicron emulsions and so on, but are all

characterized by high suspension stability due to their very small

size, which is mainly the result of substantial steric stabilization

between droplets, which explains why the Ostwald ripening process

is the only adapted droplet destabilization process. Consequently,

nano-emulsion systems can be viewed as a blueprint for the

generation of nanoparticles, even though these two phases can often

be merged into one. Thus, the countless variants of the formulation

of nanoparticles are based mainly on three different groups of

methods for nanoemulsion generation, i.e. high-energy methods,

low-energy spontaneous emulsification process. The inverse

temperature (PIT) is low-energy step process [117-119].

Advantages

1. Ease of scale-up and limited batch-to-batch variability.

2. Narrow scale nanoparticulate drug distribution.

3. Flexibility in the management of product quality.

4. Applied selectively to thermolabile compounds.

5. Taste masking.

6. Non toxic and non irritant.

7. Enhances the bioavailability of the drug.

Solid lipid nanoparticles

In 1991, Solid lipid nanoparticles were introduced and they represent

different carrier systems to traditional carriers such as liposomes,

micro and nanoparticles, emulsion [120]. As a novel colloidal drug

carrier for intravenous applications, nanoparticles made from solid

lipids are attracting great attention because they have been proposed

as an alternative particulate carrier system [121]. Solid Lipid

Nanoparticles are colloidal submicron carriers ranging from 50-1000

nm, consisting of physiological lipid, distributed in water or in an

aqueous surfactant solution [122]. SLN offers unique properties such

as small size, large surface area, high drug loading and step interaction

at the interface, and is desirable for their potential to improve

pharmaceutical performance. The use of solid lipids as the drug

delivery matrix content is well known from lipid pellets for oral drug

delivery (e. g. Mucosolvanw retardation capsules) [123].

Benefits of solid lipid nanoparticles

1. Control and target drug release from the system.

2. Brilliant biocompatibility

3. Increase steadiness of pharmaceuticals

4. Superior drug content

5. Manufacturing is much easier than biopolymeric nanoparticles.

6. Special solvent not required [124].

Nanostructure lipid carrier

Nanostructure Lipid Carriers are the second generation lipid nano

carriers consisting of solid lipid matrix filled with liquid lipids. NLCs

are able to firmly immobilize drugs and prevent particles from

coalescing as opposed to emulsions by virtue of the solid matrix.

Mobility of the drug molecules incorporated in the solid phase is also

significantly reduced. Additionally, droplets of liquid oil in the solid

matrix increase the drug load capacity relative to SLNs. NLCs also have

benefits over polymeric nanoparticles, including low toxicity,

biodegradability, drug safety, controlled release and avoidance during

development of organic solvents. NLCs have been studied intensively

as hydrophilic and hydrophobic drug delivery carriers [125].

Niosomes

Niosomes are vesicles that consist mainly of non-ionic hydrated

surfactants, in addition to cholesterol (CHOL) or its derivatives in

many cases. The specific structures of niosomes allow both

hydrophilic and lipophilic substances to be encapsulated. This can be

done by encapsulating hydrophilic substances in the vesicular

aqueous core or adsorbing them on the bilayer surfaces while the

lipophilic substances are encapsulated by partitioning them into the

bilayer's lipophilic domain. Thin lipid film or lipid cake is hydrated

and liquid crystalline bilayers stacks are liposome-forming, swelling,

and flowing. Agitation divides and self-associates the hydrated lipid

sheets to form vesicles, preventing water contact with the bilayer's

hydrocarbon center at the edges. In recent years, niosomes have

been one of the prominent vesicles in all vesicular systems, taking on

a great deal of interest as potential drug delivery systems for various

routes of administration. This is because niosomes do not have the

many drawbacks that others have and are a very effective drug

delivery system with various applications; niosomes are capable of

clogging specific types of drugs, genes, proteins and vaccines [126].

Advantages

1. Niosomes are osmotically active, chemically stable and have a

long storage time compared to liposomes.

2. Their surface formation and alteration is very simple due to

their hydrophilic head functional groups.

3. They are highly compatible with biological systems and have

low toxicity due to their non-ionic nature.

4. They are also biodegradable and non-immunogenic.

5. They can trap lipophilic drugs in aqueous compartments into

bilayer vesicular membranes and hydrophilic drugs.

6. We can enhance the therapeutic efficacy of drug molecules by

shielding the drug from the biological environment, leading to

enhanced availability and controlled drug delivery by reducing drug

effects on target cells in selected carriers and delaying circulation

clearance in sustained drug delivery.

7. Unlike phospholipids, surfactant handling does not require

special precautions and conditions.

8. Improves product bioavailability in the oral and skin.

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Int J App Pharm, Vol 12, Issue 4, 2020, 1-16

9. Niosomes can improve the absorption of certain drugs across

cell membranes, locate them in targeted tissues and avoid the

reticuloendothelial system [127-129].

Gold nanoparticles

Nanocarriers have developed a novel platform for the delivery of

therapeutic agents to specific targets [130]. Many delivery vehicles

have been developed over the last decade based on various

nanomaterials, such as polymers [131], dendrimers [132], liposomes

[133], nanotubes [134] and nanorods [135]. Gold nanoparticles

(GNPs) have recently emerged as an attractive candidate for delivering

unique payloads within their goals. The payloads may be small drug

molecules or large biomolecules, such as proteins, DNA, or vide post

RNA [136, 137]. Such therapeutic agents ' performance release is a

requirement for effective therapy. The release may be caused by

internal stimuli (e. g. glutathione (GSH) [138] or pH [139]) or external

stimuli (e. g., light [140]). For example, in the monolayer, a gold

nanoparticle with a core diameter of 2 nm could in principle be

combined with average100 molecules to available ligands. Zubarev et

al. recently succeeded in combining average70 molecules of paclitaxel,

a chemotherapy drug, with a GNP with a core diameter of 2 nm.

Quantum dots (QDs)

Quantum dots are tiny semiconductors particles a few nanometers

in size, having optical and electronic properties that differ from large

particles due to quantum mechanics. They are central topics in

nanotechnology. When UV light illuminates the quantum dots, a

quantum dot electron can be excited to a higher energy state. This

process corresponds to the transition of an electron from the

valance band to the conductance band in the case of a

semiconducting quantum point. The excited electron can drop back

into the valence band and release its energy by light emission. The

light’s color depends on the difference in energy between the

conductivity and the valance band. Nanoscale semiconductor

materials tightly contain either electrons or electron holes in the

language of materials science. Quantum dots are sometimes referred

to as artificial atoms, emphasizing their singularity, having binding,

discrete electronic states, such as atoms or molecules that occur

naturally. It has been shown that the electronic wave functions in

quantum dots are similar to those in the real atoms. By coupling two

or more such quantum dots, an artificial molecule can be made,

hybridizing even at room temperature. Quantum dots have

intermediate properties between large semiconductors and discrete

atoms or molecules. Their optoelectronic properties change as a

function of size and shape. Larger QDs with diameter of 5-6 nm emit

longer wavelengths with colors like orange or red. Smaller QDs (2-3

nm) emit shorter wavelengths, resulting in blue and green colors.

However, the specific colors vary depending on the exact

composition of the QD [141].

Example: For in vivo use of semiconductor quantum dots are imaging

of tumor vasculature, imaging of tumor-specific membrane antigens,

as well as imaging of sentinel lymph nodes. Multicolor fluorescence

imaging of cancer cells can be accomplished by systemic injection of

quatum-dot based multifunctional nanoprobes [142].

Nanoshells

Nanoshells are nanoparticles that are optically tunable and consist

of a dielectric core and a shell of thin metal. These particles can

primarily be designed to scatter or absorb light based on the

dimensions of the core and shell. A larger core results in a greater

contribution of scattering to total extinction, whereas a smaller core

typically includes absorbing properties. The location within the

spectrum of peak extinction depends on the core radius ratio to shell

thickness. A thinner shell causes the peak extinction to shift to

longer wavelengths, whereas a thicker shell produces a peak

blueshift [143]. Due to their ability to disperse or absorb light,

nanoshells have great potential for both imaging and therapeutic

applications, specifically optical imaging and photothermal tumor

ablation. Other applications include tissue welding [144] and probes

for antigen detection in whole blood [145].

Nanotues

Graphite is a well-known example of this, but now carbon can form

closed and open cages with a honeycomb arrangement beside graphite

[146]. Graphene is known in the list of carbon nanomaterials as 2D

single graphite layer. Graphene is stronger than diamond material

because it contains sp2 hybridisation that is stronger than diamond sp3

Parenteral drug delivery system

hybridisation [147]. Carbon nanotubes are among the most exciting

areas of research in recent decades [148]. Carbon nanotubes consist of

carbon, and it is a material shaped by a tube. It has too small a

diameter and is measured by nanoscale.

The term parenteral formed outside from the Greek word “para” and

intestine “enterone”. Parenterals are sterile solutions or medication

suspension in aqueous or oily vehicles. Parenteral medications are

delivered directly into lungs, muscles or under the skin, more

advanced tissues such as the spinal cord. Term used for any fluid/drug

that does not use the alimentary canal to enter the body tissue.

Pyrogens, substances causing fever, primarily lipopolysaccharides

formed by microorganism metabolism; they may be insoluble, soluble

or colloidal. Parenteral administration routes usually start more

quickly than other administration routes [149, 150].

Advantages

a) Useful for patients who are unable to take drugs orally.

b) Fast start of action.

c) Useful in emergency situations.

d) Continuous drug delivery.

e) Prevent metabolic first-passing

f) Can inject drugs directly into the tissue

g) Can be used to administer fluids

h) Electrolytes or nutrients in hospitals

i) Outpatient infusion centers and home health facilities

j) Better bioavailability

Fig. 1: Different types of routes for parenteral drug delivery

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Int J App Pharm, Vol 12, Issue 4, 2020, 1-16

Classification of parenterals

1. Small volume parenterals (SVPs)

2. Large volume Parenteral (LVPs)

1. Small volume parenterals-A small intravenous injection volume is

added to an injection packed in containers defined as 100 ml or less.

Fig. 2: Different types of small volume parenterals

Large volume parenterals

These are parenterals intended to supply air, calories, electrolytes.

These are sterile, non pyrogenic, free from particulate matter

injections having volume 101-1000 ml.

Fig. 3: Different types of large volume parenterals

Ethosomes

Touitou et al. discovered and created ethosomes in 1997 [151]. They

can be described as non-invasive new delivery carriers that allow

drugs to be transferred to and through deep skin layers and/or

systemic circulation. Ethosomes are vesicular carriers consisting of

hydroalcoholic or hydro/alcoholic/glycolic phospholipids with a

relatively high concentration or combination of alcohols [152].

These are soft, malleable vesicles that are tailored to improve the

delivery of active agents. For many years, the vesicles are well

known for their importance in cellular communication and particle

transport. Vesicles would also allow the release rate of the drug to

be regulated over an extended period of time, keep the drug

protected from immune response or other removal mechanisms and

thus be able to release the correct amount of drug and maintain the

concentration steady for a long time. The size range of ethosomes

varies from tens of nanometers (nm) to microns (μ) [153, 154].

Benefits of Ethosomes

1. Contains a mixture of non-toxic raw material.

2. Targeted drug delivery system.

3. Controlled drug delivery system.

4. The ethosomal technology is immediately available for marketing.

5. Good compliance with patients: the ethosomal drug is delivered

in a semi-solid form (gel or cream) resulting in high patient

compliance.

6. Ethosomal drug delivery system can be widely used in the fields

of pharmaceutical, veterinary, cosmetic [155, 156].

Pulsatile drug delivery systems

Pulsatile drug delivery system is that system which releases the drug

in ‘pulse’ form which means a ‘lag time’ before releasing the drug and

then complete release of the drug from the system. The release of the

drug form these systems are mostly depend upon the environmental

changes in vivo. Time controlled, stimuli induced, externally regulated

systems are made to achieve this type of drug release profile. pH-

dependent systems and micro flora dependent systems are the

examples of pulsatile drug delivery systems. These types of systems

are useful in various diseases like bronchial asthma, myocardial

infarction, angina pectoris, arthritis and hypertension, because in

these diseases, the level of hormones and other factors increases and

decreases with time. So, pulsatile systems are very useful to control

the attacks at that particular time [157, 158].

Bucky balls

In September 1985 Bucky balls were first discovered

experimentally. Bucky balls are a fullerene form with Formula C60

Lymphatic carrier drug delivery system

. It

has a cage that resembles a soccer ball, consisting of twenty

hexagons and twelve pentagons, with a carbon atom with one Π

bond and two σ bonds at each corner of the structure to create a

universal vertex [159]. Fullerenes are inert and hollow, and can be

modified indefinitely. They are not absorbed when administered

orally in water-soluble form; while on the i. v. Injection, they spread

rapidly to different body tissues. They excrete via the kidney

unchanged. It was found that the acute toxicity of water-soluble

fullerenes was fairly low. All of these interesting properties offer the

possibility of using fullerenes in biology and medicinal chemistry

and promise a bright future as medicinal agents for fullerenes. Bucky

balls are the third form of carbon, and have become the most

popular science and technology molecules. Nowadays, bucky balls

are a key topic in nanotechnology and industrial research because of

their very practical. Fullerenes are already used in today's industry,

mostly in cosmetics, where they play a significant role as

antioxidants [160, 161].

The delivery of drugs and bioactive compounds via the lymphatic

system is complex and depends on the nature of the system

physiologically. The lymphatic path plays an important role in

transporting extracellular fluid to preserve homeostasis and moving

immune cells to injury sites, preventing first-pass metabolism and

thus serving as a bypass route for compounds with lower

bioavailability, i.e. those suffering from more hepatic metabolism.

The lymph route also provides an option for the delivery of

therapeutic molecules, such as cancer treatment drugs and the

human immunodeficiency virus, which can travel through the lymph

system [162]. The targeting of the lymph system through

subcutaneous, intestinal and pulmonary routes was assessed and

subsequently used to enhance the lymph penetration and retention

of drug molecules, minimize drug-related systemic toxicity and

increase the bioavailability of poorly soluble and unstable drugs

[163].

Intrauterine device (IUD)

An intrauterine device (IUD) is a small T-shaped birth

control device, which is placed in the woman's uterus to prevent

pregnancy. IUDs are one form of long-acting reversible birth control

(LARC). IUDs are safe and effective in adolescents as well as those

who’ve not formerly had children. Once an IUD is removed, even

after long-term use, fertility returns to normal rapidly. There are

two types IUD

Non hormonal (Copper containing IUD)

Most copper IUDs have a T-shaped frame it wound be around with

pure electrolytic copper wire and/or has copper collars (sleeves).

Garg et al.

Int J App Pharm, Vol 12, Issue 4, 2020, 1-16

The arms of the frame hold the IUD in place near the top of the

uterus., copper acts as a spermicide within the uterus by increasing

levels of copper ions, prostaglandins, and white blood cells within

the uterine and tubal fluids. The increased copper ions in the

cervical mucus inhibit the sperm's motility and viability, preventing

sperm from traveling through the cervical mucus, or destroying it as

it passes through. Copper can also alter the endometrial lining, but

studies show that while this alteration can prevent implantation of a

fertilized (blastocytes), it cannot disrupt one that has already been

implanted. It is the most effective form of emergency contraception

available. It works by preventing fertilization or implantation but

does not affect already implanted embryos. It contains no hormones,

so it can be used while breastfeeding and fertility returns quickly

after removal. Copper IUDs also last longer and are available in a

wider range of sizes and shapes compared to hormonal IUDs. The

possibility of heavier menstrual periods and more painful cramps.

Hormonal IUDs work by liberating a small amount of drug

(levonorgestrel). Each kind varies in size, amount of levonorgestrel

released, and duration. The primary mechanism of action is making

the inside of the uterus uninhabitable for sperm. They can also thin

the endometrial lining and potentially impair implantation but this is

not their usual function. Because they fine the endometrial lining,

they can also reduce or even prevent menstrual bleeding [164, 165].

CONCLUSION

Different drug delivery systems have been used to provide health

benefits to the society since decades. As the world of medicine

grows, the newer system of delivering the drugs has been

discovered to solve the problems like safety and efficacy of the

newer invented active pharmaceutical ingredients. Every coin has

two sides just like every delivery system, but to avoid those

limitations newer inventions come into this world. The newer

systems then avoid the limitations of prior systems. In the end, we

can say that the allopathic system of medicines is growing towards

new heights.

ACKNOWLEDGEMENT

Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial College of

Pharmacy, Bela, Rupnagar, Punjab, India.

FUNDING

Nil

AUTHORS CONTRIBUTIONS

All the authors have contributed equally.

CONFLICTS OF INTERESTS

Declared none

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MYRICETIN NANO-PHYTOSOMES PEEL-OFF GEL MASK FORMULATION AS ANTIOXIDANT

Article

Full-text available

Jul 2021

Objective: Peel-off gel mask is an alternative preparation which can increase the convenience of use and is expected to increase the antioxidant activity of myricetin nano-phytosomes. Myricetin has various activities, namely as a natural antioxidant, anti-inflammatory, allergy, and anti-cancer. This study aims to determine the nano-phytosome myricetin can be formulated into a gel peel-off mask, determine the concentration of PVA which has the best physical properties of the gel peel-off mask, and determine the antioxidant activity. Methods: The thin layer hydration method was used to manufacture Myricetin nano-phytosomes, then dried using the freeze-drying method. The resulting nano-phytosome characterization included particle size, polydispersion index, zeta potential and absorption efficiency. Peel-off gel mask were made with variations in the concentration of the PVA gelling agent, namely F1 3.5%, F2 7%, F3 14%. The resulting peel-off gel mask was tested for physical quality including organoleptic test, homogeneity, pH, viscosity, adhesion, drying time and testing for antioxidant activity. Results: The resulting peel-off gel mask has the good physical quality and met the existing requirements, where the different PVA concentrations resulted in different physical qualities, the higher the PVA, the faster the dry time. All three formulas exhibited very strong antioxidant activity based on DPPH assay with IC50 value of 14.8 ppm (F1), 15.37 ppm (F2), and 15.87 ppm (F3). Conclusion: Myricetin nano-phytosomes can be formulated into a gel peel-off mask, Formula 2 with a 7% concentration of PVA produces the best physical quality of the peel-off gel mask, the three gel peel-off mask formulas have excellent antioxidant activity.

Transfersomes as a Surfactant-based Ultradeformable Liposome

Article

Full-text available

Jan 2024

In the modern era, there are numerous ways for drug delivery. The change in time has led to the progress of drug delivery systems gaining significant development. Even though most of the drugs are administered orally i.e., in conventional dosage form it has its limitations too like poor patient compliance, metabolism in the liver's first passage, poor absorption, and fluctuations in plasma level.Because our skin is indeed the largest organ, transdermal medication administration has received increased attention in recent years. Many lipids nanovesicles like Liposomes, Niosome, Ethosome, and Transfersomes have been developed as a carrier for transdermal drug delivery. But out of them, Transfersomes are the ones which are of great interest as they show better permeation among all as most of the other carriers cannot pass through the stratum corneum. The method of transdermal medication administration has been used to provide controlled and targeted action and can act as topical and dermal preparation. This review provides basic information about Transfersomes, their mechanism of action, applications, and comparison with other lipid nanocarriers.

RELIABLE SPECTROSCOPIC ANALYTICAL PROCEDURE FOR QUANTITATIVE ESTIMATION OF OSIMERTINIB MESYLATE IN LIPOSOMAL DRY POWDER INHALER FORMULATION

Article

Full-text available

Mar 2023

Objective: The objective of the present study was to develop an economical UV spectrophotometric method with a simple, rapid, accurate, precise, sensitive, and reproducible for the quantitative estimation of Osimertinib Mesylate (OM) in bulk and newly prepared Liposomal Dry Powder Inhaler (LDPI) formulation which has not been reported earlier. Methods: Different dilutions were prepared in methanol in the range of 4-16 µg/ml, scanned between 400-200 nm, and determined the maximum absorbance was to confirm the drug’s λmax. Linearity, accuracy, precision, the limit of detection (LOD), and the limit of quantitation (LOQ) were used as parameters to validate the method. The concentration of the OM was calculated based on a linear regression equation of the calibration curve. Results: The UV spectrum of OM showed λmax at 267 nm and a linear calibration curve with a regression coefficient (R2) of more than 0.997. The RSD for recovery studies was found ˂ 2 % and confirmed the accuracy of the proposed method. The LOD and LOQ were observed at 0.021 µg/ml and 0.063 µg/ml, respectively for bulk and 0.056 µg/ml and 0.170 µg/ml for OM LDPI formulation. The method was found to be precise with an RSD ˂ 2 %. Conclusion: The present UV spectrophotometric method can be used to successfully estimate OM in LDPI, and there is no interference of excipients during the study. The method is validated in compliance with International Conference on Harmonization (ICH) guidelines and it should be used as a routine quality control analysis i.e., assay for such dosage forms.

Phthalate toxicity mechanisms: An update

Article

Nov 2022
Comp Biochem Physiol C Pharmacol Toxicol Endocrinol

Phthalates are one of the most widely used plasticizers in polymer products, and they are increasingly being exposed to people all over the world, generating health concerns. Phthalates are often used as excipients in controlled-release capsules and enteric coatings, and patients taking these drugs may be at risk. In both animals and human, phthalates are mainly responsible for testicular dysfunction, ovarian toxicity, reduction in steroidogenesis. In this regard, for a better understanding of the health concerns corresponding to phthalates and their metabolites, still more research is required. Significantly, multifarious forms of phthalates and their biomedical effects are need to be beneficial to investigate in the various tissues or organs. Based on these investigations, researchers can decipher their toxicity concerns and related mechanisms in the body after phthalate's exposure. This review summarizes the chemical interactions, mechanisms, and their biomedical applications of phthalates in animals and human.

Magnetic Nanoparticles: Current Advances in Nanomedicine, Drug Delivery and MRI

Article

Full-text available

Aug 2022

Cezar Comanescu

Magnetic nanoparticles (MNPs) have evolved tremendously during recent years, in part due to the rapid expansion of nanotechnology and to their active magnetic core with a high surface-to-volume ratio, while their surface functionalization opened the door to a plethora of drug, gene and bioactive molecule immobilization. Taming the high reactivity of the magnetic core was achieved by various functionalization techniques, producing MNPs tailored for the diagnosis and treatment of cardiovascular or neurological disease, tumors and cancer. Superparamagnetic iron oxide nanoparticles (SPIONs) are established at the core of drug-delivery systems and could act as efficient agents for MFH (magnetic fluid hyperthermia). Depending on the functionalization molecule and intrinsic morphological features, MNPs now cover a broad scope which the current review aims to overview. Considering the exponential expansion of the field, the current review will be limited to roughly the past three years.

Recent Developments in Medicated Lozenges: A Promising Dosage Form for the Effective Delivery of Therapeutic Agents

Article

Jun 2021

Background The delivery of therapeutic agents through the oral route remains the most favorable one as compared to other routes of drug administration. However, numerous disadvantages are encountered in conventional formulations such as low bioavailability, first-pass metabolism, gastric irritation, delayed onset of action, bitter taste, low retention time, frequent dosing, and non-localized drug targeting. All these problems encountered guide the various pharmaceutical industries to manufacture and develop a novel solid oral dosage form called lozenges. Lozenges are solid oral dosage forms of medicament, meant to be dissolved within the mouth or pharynx. It may consist of one or more than one medicinal agent contained in a sweetened and flavored base material. Objective The present review is focused on various types, compositions, methodologies used to prepare the medicated lozenges and on different evaluation parameters that establish its safety and efficacy. It also put a light on different commercially available and reported medicated lozenges formulation. Method The various review and research articles reported by different researchers were studied extensively by using the databases of Google Scholar, Pubmed, Scopus, Web of Science and various commercial websites that were also investigated for information regarding new products. Results Lozenges provides various advantages in terms of patient compliance, rapid onset of action, prolonged retention time, enhancement of bioavailability, ease of manufacturing, localized drug targeting, sustained or controlled effect, and reduced dosing frequency. It has also the ability to incorporate the drugs belong to different therapeutic classes for treating various disorders related to oral cavities like gingivitis, dental plaque, mouth ulcers, throat pain, oral thrush, throat infection, periodontitis, and pharyngitis. However, its applicability is not only limited to localized action, but it has also been employed to deliver the drug systemically for the conditions such as cough, decongestion, runny nose, nausea, vomiting, allergy, low immunity, fever, body ache, the killing of worms and smoking cessation. Conclusion It was concluded that it has been played an important role in the field of drug delivery and will continue to perform in the same way in the future as well.

GREEN SYNTHESIS OF SILVER NANOPARTICLES (AgNPs) USING HELVELLA LEUCOPUS PERS. AND THEIR ANTIMYCOTIC ACTIVITY AGAINST FUNGI CAUSING FUNGAL ROT OF APPLE

Article

Full-text available

Feb 2020

Objectives: The main objective of the present study was to synthesize silver nanoparticles (AgNPs) by green approach using Helvella leucopus and to evaluate the antimycotic activity of synthesized AgNPs against fungi causing fungal rot of apple. Methods: During the present study for green synthesis of AgNPs using H. leucopus, equal volumes of both mushroom extract (100 ml) and silver nitrate solution (100 ml) were mixed and incubated at room temperature for the bioreduction process. These synthesized AgNPs were characterized by ultraviolet-visible spectroscopy, scanning electron microscopy, Fourier transmission infrared spectroscopy, and X-ray diffraction analysis. Furthermore, these synthesized AgNPs were evaluated for their antimycotic activity by spore germination method and agar well diffusion assay against different tested fungi. Results: The results revealed that strong plasmon absorbance band was observed at 420 nm which confirms the synthesis of AgNPs using H. leucopus. The synthesized AgNPs were spherical in aggregated form with size ranging from 80 to 100 nm. Furthermore, different concentrations of synthesized AgNPs caused significant inhibition in spore germination and reduction in zone of inhibition of tested fungal pathogens. The highest inhibition in spore germination by AgNPs at highest concentrations was observed against Penicillium chrysogenum followed by Aspergillus niger and Alternaria alternata, respectively. Similarly, the synthesized AgNPs at highest concentrations showed maximum zone of inhibition against P. chrysogenum followed by A. niger and A. alternata, respectively. Conclusion: It is concluded from the present study that synthesized AgNPs have good potential to be used as antifungal agents against many fungal plant pathogens. The synthesized AgNPs using mushroom fungi also have potential for the development of nanofungicides against fungal pathogens but after proper investigation.

PREPARATION AND CHARACTERIZATION OF ANCHOVY (STOLEPHORUS SP) PROTEIN CONCENTRATE NANOPARTICLE USING IONIC GELATION METHOD

Article

Full-text available

Feb 2020

Objective: Nanoparticle preparation can increase the bioavailability of anchovy protein. This study aims to optimize and characterize anchovy protein concentrate nanoparticle based on volume comparison of chitosan-TPP (Tripolyphosphate) matrix in forming the size of anchovy protein concentrate nanoparticle with ionic gelation method. Methods: Fresh anchovy was extracted by an acid-base method using solvents of NaOH and HCl to get protein concentrate. After that, it was conducted by formulating anchovy protein concentrate into a mixture of chitosan-TPP matrix with volume ratio which was divided into 5 series of variations, namely F1 without matrix, F2 1:1, F3 1:3, F4 1:5 and F5 1:7 ratio of chitosan to TPP, then formed matrix was determined the value of the encapsulation efficiency and characterized using a particle size analysis tool. Results: The results showed that the optimum volume comparison of the chitosan-TPP matrix in forming nanoparticle of anchovy protein concentrate was ratio 1:7 because this has a matrix encapsulation efficiency value of 99.11%, a small particle concentrate size of 687.26 nm, a good polydispersity index value of 0.406 and a value of zeta potential of+12.9 mV. Conclusion: The optimum formula of the chitosan-TPP matrix volume ratio in forming anchovy protein concentrate nanoparticle is F5 with the ratio of chitosan-TPP matrix mixture 1:7.

A REVIEW ON PHYSICO-CHEMICAL PARAMETERS OF LIPOSOMAL DOXORUBICIN

Article

Full-text available

Dec 2019

The development of a generic liposomal doxorubicin product requires the study of critical physicochemical properties of the formulation. Food and Drug Administration (FDA) draft guideline has suggested few parameters to be tested for in vitro bioequivalence study which include liposomal composition, state of encapsulated drug, internal environment, liposomal morphology and number of lamellae, lipid bilayer phase transition, liposomal size distribution, grafted Polyethylene Glycol (PEG) at liposomal surface, electric surface potential or charge and in vitro leakage under multiple conditions. Characteristic features of components of liposomal doxorubicin formulation and detail of parameters to be studied have been discussed. This review compile specific, current and historical research outcomes on in vitro analysis of liposomal doxorubicin and highlights the important features that have a critical impact on properties of liposomal doxorubicin formulation. It will provide a better insight to the generic manufacturers and will help them to identify the critical quality attributes during the formulation development phase.

Investigative Study on Impact of Solid: Liquid Lipid Ratio and Stabilizer Amount on Some Characteristics of Nanostructure Lipid Carriers of Quetiapine Fumarate

Article

Full-text available

Nov 2019

Quality by Design Approach for Development and Characterization of Solid Lipid Nanoparticles of Quetiapine Fumarate

Article

Full-text available

Jul 2019

Background Quetiapine fumarate, a 2nd generation anti-psychotic drug has oral bioavailability of 9% because of extensive hepatic first pass metabolism. Reports suggest that co-administration of drugs with lipids affects their absorption pathways, enhances lymphatic transport thus bypassing hepatic first pass metabolism resulting in enhanced bioavailability. Objective The present work was attempted with the aim of developing and characterising potentially lymphatic system absorbable solid lipid nanoparticles (SLN) of Quetiapine fumarate (QF) by Quality by Design approach. Method Hot emulsification followed by ultrasonication was used as method of preparation. Precirol ATO5, Phospholipon 90G and Poloxamer 188 were used as lipid, stabilizer and surfactant respectively. A 32 Central Composite design (CCD) optimised the 2 independent variables, lipid concentration (X1) and stabilizer concentration (X2) and assessed their effect on percent Entrapment Efficiency (%EE: Y1). The SLN, lyophilized using mannitol, were studied for stability at 5οC ±3 οC and 25 ± 2οC/60 ± 5% RH for 3 months. Results The optimised formula derived for SLN had 270mg PrecirolATO5 and 107mg of Phospholipon 90G giving %EE of 76.53%. Mean particle size was 159.8nm with polydispersity index 0.273 and zeta potential -6.6mV. In-vitro drug release followed Korsmeyer-Peppas kinetic model (R2=0.917) with release exponent n=0.722 indicating non-Fickian diffusion . TEM images exhibited particles to be spherical and smooth. FTIR, DSC and XRD studies ascertained drug-excipient compatibility. Stability studies suggested 5οC as appropriate temperature for SLN storage preserving important characteristics within acceptable limits. Conclusion Development and optimisation by Quality by Design was justified as it yielded SLN having acceptable characteristics and potential application for intestinal lymphatic transport.

Recent advances in the development of gene delivery systems

Article

Full-text available

Mar 2019

Background Gene delivery systems are essentially necessary for the gene therapy of human genetic diseases. Gene therapy is the unique way that is able to use the adjustable gene to cure any disease. The gene therapy is one of promising therapies for a number of diseases such as inherited disorders, viral infection and cancers. The useful results of gene delivery systems depend open the adjustable targeting gene delivery systems. Some of successful gene delivery systems have recently reported for the practical application of gene therapy. Main body The recent developments of viral gene delivery systems and non-viral gene delivery systems for gene therapy have briefly reviewed. The viral gene delivery systems have discussed for the viral vectors based on DNA, RNA and oncolytic viral vectors. The non-viral gene delivery systems have also treated for the physicochemical approaches such as physical methods and chemical methods. Several kinds of successful gene delivery systems have briefly discussed on the bases of the gene delivery systems such as cationic polymers, poly(L-lysine), polysaccharides, and poly(ethylenimine)s. Conclusion The goal of the research for gene delivery system is to develop the clinically relevant vectors such as viral and non-viral vectors that use to combat elusive diseases such as AIDS, cancer, Alzheimer, etc. Next step research will focus on advancing DNA and RNA molecular technologies to become the standard treatment options in the clinical area of biomedical application.

Microneedles: A smart approach and increasing potential for transdermal drug delivery system

Article

Full-text available

Jan 2019
BIOMED PHARMACOTHER

The most widely used methods for transdermal administration of the drugs are hypodermic needles, topical creams, and transdermal patches. The effect of most of the therapeutic agents is limited due to the stratum corneum layer of the skin, which serves as a barrier for the molecules and thus only a few molecules are able to reach the site of action. A new form of delivery system called the microneedles helps to enhance the delivery of the drug through this route and overcoming the various problems associated with the conventional formulations. The primary principle involves disruption of the skin layer, thus creating micron size pathways that lead the drug directly to the epidermis or upper dermis region from where the drug can directly go into the systemic circulation without facing the barrier. This review describes the various potential and applications of the microneedles. The various types of microneedles can be fabricated like solid, dissolving, hydrogel, coated and hollow microneedles. Fabrication method selected depends on the type and material of the microneedle. This system has increased its application to many fields like oligonucleotide delivery, vaccine delivery, insulin delivery, and even in cosmetics. In recent years, many microneedle products are coming into the market. Although a lot of research needs to be done to overcome the various challenges before the microneedles can successfully launch into the market.

Transferosomes: A Novel Ultradeformable Vesicular Carrier for Transdermal Drug Delivery

Article

Jan 2022

Pulsatile Drug Delivery Systems: An Overview

Article

Nov 2009

Pulsatile Drug Delivery Systems are gaining a lot of interest as they deliver the drug at the right place at the right time and in the right amount, thus providing spatial and temporal delivery and increasing patient compliance. These systems are designed according to the circadian rhythm of the body. The principle rationale for the use of pulsatile release of the drugs is where a constant drug release is not desired. A pulse has to be designed in such a way that a complete and rapid drug release is achieved after the lag time. Various systems like capsular systems, osmotic systems, single- and multiple-unit systems based on the use of soluble or erodible polymer coating and use of rupturable membranes have been dealt with in the article. It summarizes the latest technological developments, formulation parameters, and release profiles of these systems. These systems are beneficial for the drugs having chronopharmacological behavior where night time dosing is required, such as anti-arhythmic and anti-asthmatic.

A REVIEW OF PELLETS AND PELLETIZATION PROCESS - A MULTIPARTICULATE DRUG DELIVERY SYSTEM

Article

Nov 2018

Vijaya Kanagala

A COMPLETE AND UPDATED REVIEW ON VARIOUS TYPES OF DRUG DELIVERY SYSTEMS

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