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Walia et al Journal of Drug Delivery & Therapeutics. 2021; 11(6):257-264
ISSN: 2250-1177 [257] CODEN (USA): JDDTAO
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Open Access to Pharmaceutical and Medical Research
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Open Access Full Text Article Review Article
A Novel Drug Delivery of Microspheres
Walia Smily*1, Dua J.S.1, Prasad D.N.2
1 Department of Pharmaceutics, Shivalik College of pharmacy, Nangal, Punjab, India
2 Department of Pharmaceutical Chemistry, Shivalik College of pharmacy, Nangal, Punjab, India
Article Info:
_________________________________________
Article History:
Received 21 September 2021
Reviewed 28 October 2021
Accepted 03 November 2021
Published 15 November 2021
_________________________________________
Cite this article as:
Walia S, Dua JS , Prasad DN, A Novel Drug Delivery
of Microspheres, Journal of Drug Delivery and
Therapeutics. 2021; 11(6):257-264
DOI: http://dx.doi.org/10.22270/jddt.v11i6.5059
_________________________________________
*Address for Correspondence:
Walia Smily, Department of Pharmaceutics, Shivalik
College of pharmacy, Nangal, Punjab, India
Abstract
______________________________________________________________________________________________________
Microspheres are multiparticulate drug delivery systems that distribute medications at a
predetermined rate to a specific region. Microspheres are free-flowing powders
manufactured from biodegradable proteins or synthetic polymers, with particle sizes ranging
from 1 to 1000 micrometers. Benefits of using microspheres in medication delivery, bone
tissue manufacture, and pollutant absorption and desorption by regeneration .The study
demonstrates how microsphere parameters are planned and measured. Bioadhesive
microspheres, polymeric microspheres, magnetic microspheres, floating microspheres, and
radioactive microspheres are only a few examples of complicated microspheres. Cosmetics,
oral medication administration, target drug delivery, ocular drug delivery, gene delivery, and
other industries covered in the paper could all benefit from microspheres. To ensure best
therapeutic effectiveness, the agent must be delivered to target tissue at an optimal amount
during the appropriate timeframe, with low toxicity and adverse effects. There are several
methods for delivering the therapeutic substance to the target site in a controlled manner.
The use of microspheres as medication carriers is one such technique. The value of
microspheres as a novel drug delivery carrier to accomplish site-specific drug delivery was
discussed in this article.
Keywords: Microspheres, method of preparations, polymer bioadhesion, types of
microspheres.
INTRODUCTION:
The purpose of the novel drug delivery system is to
distribute medications at a rate that is appropriate for the
body's needs throughout therapy, while also getting the
active component to the site of action as rapidly as feasible.
The capacity of drug delivery systems (DDS) to precisely
monitor drug release rates or target medications to specific
body regions has had a significant impact on the health-care
system. The finest drug delivery system provides
pharmaceuticals at a defined pace determined by the body's
demands and delivers active components to the site of action
over the duration of treatment. Drug carrier technology
offers an intelligent approach by binding the drug to carrier
particles such as microspheres, nanoparticles, or lipids to
drug delivery.1
MICROSPHERES:
Entrapped substances are scattered within the
microsphere's matrix in micromatrices, while entrapped
substances are clearly confined by the characteristic capsule
wall in microcapsules. Micromatrices have the trapped
material spread throughout the microspheres matrix, while
microcapsules have the trapped substance clearly confined
by a defined capsule wall. The medication was disseminated
or dissolved via the particle matrix, and the solid
biodegradable microspheres have the potential to allow for
regulated drug release. Microspheres are solid spherical
particles that range in diameter from 1 to 100µm. They're
biodegradable, spherical, free-flowing proteins or synthetic
polymer particles. 2 Microspheres are divided into two
categories;
Microcapsule
Micro matrices
Microcapsules have a distinct capsule wall around the
entrapped substance, whereas micromatrices have the
entrapped substance spread throughout the matrix of the
microsphere. Solid biodegradable microspheres with a drug
disseminated or dissolved via a particle matrix can be used
to provide controlled drug release. Biodegradable synthetic
polymers and modified natural goods, as well as polymeric
waxy or other protective compounds, are used to make them.
3 Polymers and waxes of natural and manmade sources are
used to make them. Microsphere stability, solubility, and
drug release are all affected by the type of polymer employed
to form them. Polyethylene, polystyrene, and expandable
microspheres are the most common types of polymeric
microspheres. Solid and hollow microspheres are available.
Hollow microspheres are used as an addition to lower the
density of a material. Topical formulations based on
microspheres have gained popularity for their therapeutic
efficacy over longer periods of time. In recent years, the
usage of micro particle medication delivery devices has
grown in popularity.4,5,6,7,8
Walia et al Journal of Drug Delivery & Therapeutics. 2021; 11(6):257-264
ISSN: 2250-1177 [258] CODEN (USA): JDDTAO
HISTORY
Bunge berg de Jong and coworkers' work on the
trapping of substance using coacervates in the 1930s
gave birth to the concept of packaging minuscule
quantities of stuff in microspheres.
Microspheres were first used in industry in the 1960s.9
ADVANTAGES OF MICROSPHERES10
1. Microspheres have a predictable and long-term
therapeutic effect.
2. Lower the frequency of dosing to increase patient
compliance.
3. They can be introduced into the body due to their
spherical shape and lower size.
4. Better drug use will increase bioavailability while
reducing the likelihood of negative effects.
5. Microsphere shape enables for regulated medication
release and degradation variations.
6. Oils and other liquids are solidified to make them more
manageable.
7. Compared to big polymer implants, biodegradable
microspheres have the benefit of not requiring surgical
procedures for installation and removal.
DISADVANTAGES OF MICROSPHERES:
1. The ingredients and processing costs of controlled
release formulations are significantly greater than
regular formulations.
2. The fate of polymer matrix and its environmental impact.
3. Plasticizers, stabilizers, antioxidants, and fillers are
examples of polymer additives.
4. Reproducibility is less.
5. Process variables such as temperature, pH, solvent
addition, and evaporation/agitation might affect the
stability of encapsulated core particles.
6. The influence on the environment of polymer matrix
breakdown products produced in reaction to heat,
hydrolysis, oxidation, solar radiation, or biological
agents.
IDEAL CHARACTERSTICS OF MICROSPHERES:
11
1. The ability to assimilate medication concentrations that
are relatively high.
2. After synthesis, the preparation's stability and shelf life
must be clinically acceptable.
3. Injections in aqueous vehicles with controlled particle
size and dispersibility.
4. Controlled release of active substances over a long
period.
5. Controllable biodegradability and biocompatibility
6. Susceptibility to chemical modification.
CRITERIA FOR MICROSPHERES
PREPARATION: 11
It is possible to incorporate liquid, solid, or gas into one
or more polymeric coatings using the microencapsulation
technique.
The different methods for preparing various
microspheres are dependent on the route of
administration , particle size , drug release length and the
rpm, cross linking process, drug of cross linking , co
precipitation , evaporation time , and other factors.
The preparation of microspheres should satisfy certain
criteria:
o The release of active reagent under strict supervision on
a long time scale.
o It should be capable of incorporating very high drug
concentrations.
o It should be able to withstand chemical alteration.
o After synthesis, the consistency of the preparation for a
clinically suitable shelf life.
o Biodegradability and controllable biocompatibility.
The controlled particle size and dispersabilty in the
aqueous vehicles for injection.
Figure 1: Microspheres and Microcapsules
Walia et al Journal of Drug Delivery & Therapeutics. 2021; 11(6):257-264
ISSN: 2250-1177 [259] CODEN (USA): JDDTAO
CLASSIFICATION OF POLYMERS:
Synthetic Polymers: Divided into two types:
Non – biodegradable: Acrolein, glycidyl methacylate,
Epoxy polymers etc.12
Biodegradable: Polyanhydrides, polyalkylcyanoacrylates
lactides glycosides and their copolymers.13,14
Natural Materials: They are obtained from different
sources like: 15,16
Proteins (albumin, gelatin, collagen)
Carbohydrates (starch, agarose, carrageenan)
Chemically modified carbohydrates (poly acryl dextran,
poly acryl starch)
TYPES OF MICROSPHERES:
Bioadhesive Microspheres
The technique of adhering a medication to a membrane
using the adhesive characteristics of water-soluble polymers
is known as adhesion. A drug delivery system's adhesion to a
mucosal membrane, such as the buccal, ocular, rectal, nasal,
and other mucosal membranes, is referred to as bio
adhesion. These microspheres have a longer residence time
at the application site, resulting in better absorption and
therapeutic activity.17
Magnetic Microspheres
This type of delivery mechanism is crucial because it allows
the drug to be administered precisely where it is required. In
this situation, a smaller quantity of magnetically focused
medicine will replace a larger quantity of freely circulating
drug. Magnetic responses to a magnetic field can be found in
chitosan, dextran, and other integrated materials utilized in
magnetic microspheres.18 The different types are:
Therapeutic Magnetic Microspheres
These are used to deliver a chemotherapeutic drug to
malignancies in the liver. This technique can potentially be
used to target drugs like proteins and peptides.17
Diagnostic Microspheres
By producing nano-size particles of paramagnetic iron
oxides, they can be used to image liver metastases as well as
distinguish bowel loops from other abdominal structures.19
Floating Microspheres
Floating forms have a lower bulk density than gastric fluid;
therefore they float in the stomach and have no effect on the
rate of gastric emptying. The medicine is released slowly and
at the desired rate if the system is floating on gastric
contents, which enhances stomach residency and plasma
concentration variability. Strikes are also less common, as is
dose dumping. It also offers a longer therapeutic effect,
reducing the need for frequent dosage.20
Radioactive Microspheres
Radioembolization is a type of treatment that involves
injecting a substance into the body. Microspheres with a
diameter of 10-30nm are larger than capillary microspheres
and are tapped in the first capillary bed as they pass through
before being introduced into the arteries that create a tumor
of interest. As a result, radioactive microspheres deliver a
high dosage of radiation to the target locations while causing
no harm to the surrounding tissues in all of these scenarios.
21 It differs from a drug delivery system in that radioactivity
is not released from microspheres but instead acts from
within a radioisotope typical distance, and the various types
of radioactive microspheres are α,γ,β emitters.22
Polymeric Microspheres
The different types of polymeric microspheres can be
classified as:
Biodegradable Polymeric Microspheres
Biodegradable, biocompatible, and bioadhesive natural
polymers such as starch are employed. Biodegradable
polymer extends the residency period when in touch with
mucous membranes due to its excellent degree of swelling in
an aqueous media, resulting in the development of gels. The
rate and degree of medication release are controlled by the
polymer concentration and the release pattern throughout
time. The key problem is that biodegradable microspheres'
drug loading performance in clinical application is tricky,
making drug release difficult to control. Microspheres, on
the other hand, offer a wide range of uses in microsphere-
based therapy.23
Synthetic Polymeric Microspheres
Synthetic polymeric microspheres have been proved to be
safe and biocompatible in clinical applications as bulking
agents, fillers, embolic particles, drug delivery vehicles, and
other applications.24 The main disadvantage of these
microspheres is that they have a proclivity for moving away
from the injection site, providing a danger of embolism and
subsequent organ injury.
MECHANISM OF MICROSPHERES
The majority of drug delivery using micro particles avoids
the establishment of a matrix-like internal solid dispersion
morphological structure. It's possible that the medication is
insoluble in the polymeric matrix and is released during
erosion. Water diffuses into the matrix first, causing it to
dissolve towards the device's surface. The osmotic pressure
is relieved by establishing a conduit to the surface and
releasing a predefined amount of medicine in the initial drug
burst.25
METHOD OF PREPARATION
Methods used for the preparation of microspheres are:
Single emulsion techniques
Double emulsion techniques
Polymerization
Normal polymerization
Interfacial polymerization
Phase separation coacervation technique
Spray drying
Emulsion cross linking method
Solvent evaporation
Solution –enhancement dispersion method
Ionic gelation method26
Single Emulsion Technique
A wide range of proteins and carbs can be prepared using
this technology. The natural polymers are dispersed in an oil
phase, which is a non-aqueous media, after being dissolved
in an aqueous medium. That is the first stage of the
procedure.27 The two methods are used to cross link the
next step as:
Walia et al Journal of Drug Delivery & Therapeutics. 2021; 11(6):257-264
ISSN: 2250-1177 [260] CODEN (USA): JDDTAO
Cross Linking by Heat
It can be done by dispersing the dispersion in hot oil.
However it is not suited for thermo sensitive medications.
Chemical Cross Linking Agents
Formaldehyde, diacid chloride, glutaraldehyde, and other
substances are used in this process. When active ingredients
are administered at the time of preparation and
subsequently centrifuged, washed, and separated, it is
detrimental to the unnecessary exposure of active
substances to chemicals. By introducing a chitosan solution
(in acetic acid) to liquid paraffin containing a surfactant
without using an emulsion as a cross-linking agent, a 25%
glutaraldehyde solution is used to make microspheres.28
Double Emulsion Technique
The primary w/o emulsion is poured into an aqueous
polyvinyl alcohol solution, resulting in W/O/W. For 30
minutes, the w/o/w emulsion must be stirred continuously.
For 30 minutes, gradually add water to the emulsion.
Filtration and drying of microcapsules under vacuum Water-
soluble medications, peptides, proteins, and vaccines are all
well-suited to it. This procedure can be done with both
natural and synthetic polymers. In a continuous organic
lipophilic phase, the aqueous protein solution is dispersed.30
Polymerization Techniques
Two techniques are mainly used for the formulation of
microspheres are as follow;
Normal Polymerization
A monomer or a combination of monomers, along with the
initiator or catalyst, is commonly heated to commence
polymerization in bulk polymerization. The resulting
polymer can be molded into microspheres. Drugs can be
added during the polymerization process. Although this is a
pure polymer production technique, it is difficult to dissipate
the heat of the reaction, which can harm thermo labile active
components. Suspension polymerization, also known as
pearl polymerization, involves heating the monomer
combination with the active medication as droplets
dispersion in a continuous aqueous phase at a lower
temperature.31
Interfacial Polymerization
At the interface between the two immiscible liquid phases,
different monomers react to generate a polymer film that
basically envelops the dispersed phase. This effectively
encloses the dispersed phase. Two reactive monomers are
used in this process; one is dissolved in the continuous
phase, while the other is disseminated in the continuous
phase (naturally aqueous) throughout which the second
monomer is emulsified.32
Phase Separation Coacervation Technique
This method is based on the idea of lowering the polymer's
solubility in the organic phase in order to affect the
production of coacervates, a polymer-rich phase. The drug
particles are disseminated in a polymer solution, and the
device is then filled with an incompatible polymer that
separates the first polymer phase and engulfs the drug
particles. The addition of the non-solvent causes the
polymer to solidify. Using butadiene as an incompatible
polymer, this method was utilized to make polylactic acid
(PLA) microspheres. The pace of accomplishment of the
coacervates determines the distribution of the polymer film,
hence process variables are important. The particle size and
aggregation of the produced particles are both important
factors. Because as the process of microsphere formation
begins, the produced polymerized globules begin to stick
and form agglomerates, agglomeration must be avoided by
stirring the suspension with an appropriate speed stirrer.
Process variables are crucial because they govern the
kinetics of the produced particles, as there is no
predetermined state of equilibrium.32
Spray Drying
Before being spray dried, the polymer is first dissolved in a
suitably volatile organic solvent, such as dichloromethane or
acetone. After that, high-speed homogenization is used to
disseminate the chemical in a polymer solution. After that,
the dispersion is atomized, resulting in a heated air current.
The atomization process produces tiny droplets or fine mists
from which the solvent evaporates almost instantly, forming
microspheres in the 1-100 nm range. By a cyclone separator,
micro particles are separated from hot air, and the solvent
residue is removed using vacuum drying. The procedure's
survivability under aseptic circumstances is one of its key
advantages. This is a fast process that results in the
production of porous micro particles.33
Emulsion Crosslinking Method
The reactive functional group of polymers is used to
crosslink with the aldehyde group of cross linking agents in
this procedure. Emulsifying the polymer aqueous solution in
the oily phase yield water-in-oil emulsion in this approach. A
appropriate sulphosuccinate was used to stabilize aqueous
droplets. To harden the droplets, a cross linker such as
glutraldehyde was added to the stable emulsion. To
eliminate residues of oils, the microspheres were filtered
and washed repeatedly with hexane or petroleum ether.
They were eventually washed with water to remove the
cross linker, and then dried for 24 hours at room
temperature.34
Solvent Evaporation
A liquid production vehicle is used to carry out the
processes. A volatile solvent is used to disperse the
microcapsules, which is not mixed with the liquid stage of
the manufacturing process. The microencapsulated core
material is dissolved or dispersed in a polymer coating
solution with agitation. The core material mixture is spread
during the vehicle's liquid production process to achieve the
appropriate microcapsule size. The combination is then
heated, if possible, to evaporate the solvent for the primary
material's polymer dispersion in the polymer solution, and
the polymer shrinks around the core. A matrix – a type of
microcapsule – is formed when the core material is
dissolved in a polymer coating solution. Water-soluble or
water-insoluble core materials are available. Aqueous (o/w)
or non-aqueous formations result from solvent
evaporation.35
Ionic Gelation Method
The alginate/chitosan particulate system was created using
this approach for the release of diclofenac sodium. The
medication is mixed with an aqueous sodium alginate
solution in this stage. To obtain a full solution, the stirring is
continued and the Ca2+/Al3+ solution is added drop by drop.
Internal jellification was achieved by leaving the
microspheres in the original solution for 24 hours before
filtration and separation. PH 6.4-7.2 allows for full release,
but the drug will not release at an acidic pH.36
Walia et al Journal of Drug Delivery & Therapeutics. 2021; 11(6):257-264
ISSN: 2250-1177 [261] CODEN (USA): JDDTAO
LIST OF MARKETED MICROSPHERES DRUG PRODUCT37
Table 1: Marketed Microspheres Drug Products
DRUG
COMMERCIAL NAME
TECHNOLOGY
Risperidone
Risperdal IR, Consta
Double emulsion(o/w)
Naltrexon
Vivitro IR
Double emulsion(o/w)
Leuprolide
Leupron DepotR
Double emulsion(o/w/o)
Octreotide
SandostatinR LAR
Phase separation
Somatropin
NutropinR
Spray drying
Triptorelin
Trelstar Depot, DecapeptylIR SR
Phase separation
Lanreotide
SomatulineR LA
Phase separation
EVALUATION PARAMETERS OF
MICROSPHERES:
Characterization
The characterization of micro particulate carriers is an
important phenomenon that contributes in the development
of a suitable carrier for the transport of proteins, medicines,
or antigens. These microspheres have different
microstructures. These microstructures control the carrier's
release and stability.38
Particle size and shape:
Conventional light microscopy (LM) and scanning electron
microscopy (SEM) are the most widely utilized technologies
for seeing tiny particles. Both can be used to investigate the
form and structure of micro particles. In the case of double-
walled microspheres, LM allows you to modify the coating
settings. Before and after coating, the microspheres'
structures can be viewed, and the difference may be assessed
microscopically. In comparison to LM, SEM has a better
resolution. SEM can be used to investigate the surfaces of
microspheres, and it can also be used to investigate double-
walled structures when the particles are cross-sectioned.38
Electron spectroscopy for chemical analysis
Electron spectroscopy for chemical analysis (ESCA) can be
used to determine the surface chemistry of microspheres.38
Density Determination
A multi-volume pycnometer can be used to calculate the
density of the microspheres.39
Iso electric point
Micro-electrophoresis is used to determine the
electrophoretic mobility of microspheres, which can then be
used to determine the isoelectric point.40
Angle of contact
The wetting qualities of the micro particle carrier are
determined by the contact angle.41
Percentage yield
It is computed by multiplying the weight of microspheres
obtained from each batch by the total weight of medication
and polymer used to prepare that batch by 100.43
Swelling Index
The swelling index of the microspheres was determined by
using the formula:
Swelling Index= (mass of swollen microspheres mass of dry
microspheres /mass of dried microspheres) 43
Bulk Density:
It's calculated by pouring a known-weight sample of
microspheres into a measuring cylinder, measuring the
length of the cylinder, and then dividing the weight by
volume.
Bulk Density =wt. of the microspheres/bulk volume
Tapped Density
It's calculated by pouring a known-weight sample of
microspheres into a measuring cylinder, tapping it
completely, and measuring the volume, then dividing the
weight by the volume.
Tapped density = wt. of the microspheres/ volume after
tapping
Hausner`s Ratio
The ratio of tapped density to bulk density of microspheres
is known as Hausner's ratio, and it can be used to forecast
how microspheres would flow. The presence of free-flowing
microspheres is indicated by a low Hausner's ratio of 1.2.
Hausner`s ratio= bulk density- tapped density
Angle of repose
A heap of microspheres can achieve the highest angle to the
horizontal. One of the approaches for estimating the angle of
repose is to use a set height cone and a fixed base cone.
Angle of repose Ɵ= tan-1h/r
r= the radius of the base of the heap of a microspheres
h= height of the heap of microspheres
Zeta Potential
The polyelectrolyte shell is formed by combining different
atomic loads of chitosan in the W2 stage, and the succeeding
particles are determined by Zeta potential estimate.46
APPLICATIONS OF MICROSPHERES49, 50
Microspheres in vaccine delivery
The following requirements must be met by an ideal vaccine:
effectiveness, safety, convenience of use, and affordability.
Walia et al Journal of Drug Delivery & Therapeutics. 2021; 11(6):257-264
ISSN: 2250-1177 [262] CODEN (USA): JDDTAO
Biodegradable vaccine delivery systems for vaccines given
via the parental route may be able to overcome the
drawbacks of traditional vaccines.
Improved antigen city by adjuvant action
Modulation of antigen release
Stabilization of antigen.
Targeting using micro particulate carriers
The concept of site-specific medication delivery, often known
as targeting, is a well-established doctrine that is gaining
traction. The ability of a medication to reach and interact
with its target receptors determines its therapeutic
effectiveness. At the heart of pharmacological action, which
is mediated via a carrier system, is the ability to leave the
pool in a repeatable, effective, and exact manner.
Monoclonal antibodies mediated microspheres
targeting
Monoclonal antibodies directed against microspheres are
known as immune microspheres. This is a method of
attaining site-specific targeting. Monoclonal antibodies are
highly selective molecules. Mabs can be directly linked to the
microspheres thanks to covalent binding. Mabs can be
connected to microspheres using any of the ways described
below.
Non – specific adsorption and specific adsorption
Direct coupling
Coupling via reagents
Chemoembolisation
Chemoembolisation is an endovascular treatment that
involves targeted tumor artery embolization and local
delivery of a chemotherapeutic medication at the same time
or later.
Imaging
The particle size range of microspheres is an important
consideration when imaging specific regions with radio-
labeled microspheres. The particle is caught in the lungs
capillary bed after being introduced intravenously outside of
the portal vein. This phenomenon is used to create
scintigraphic imaging of tumor masses in the lungs using
tagged human serum albumin microspheres.
Topical porous microspheres
Micro sponges are porous microspheres with an
interconnected network of voids ranging in size from 5 to
300µm. The topical carry system is made up of micro
sponges that can entrap a wide range of active compounds
like emollients, perfumes, and essential oils, among others.
Medical Applications
Microspheres are utilized in vaccine administration for
diseases such as hepatitis, influenza, pertusis, diphtheria, and
many others, and have a wide range of medical applications,
including long-term release of proteins, hormones, and
peptides. For DNA plasmid and insulin delivery therapy,
microspheres are the most effective. Through intra arterial/
intravenous treatments, microspheres will be used to target
leaky tumor arteries passively and tumor cells and antigens
dynamically.
Radioactive Microspheres Applications
It can be utilized for radio embolization of liver and spleen
tumors, as well as radio synovectomy of rheumatic joints,
local radiotherapy, and interactivity care. In a deep vein
thrombosis, the liver, spleen, bone marrow, lung, and even
the thrombus can be imaged.
Other Application
Fluorescent microspheres can be employed in membrane-
based flow cytometry, cell biology, and fluorescent
immunosorbent assays, among other things. Yttrium 90 can
be used for both primary and pre-transplant management of
HCC, according to promising data.
Colonic Drug Delivery
Chitosan, for example, has been utilized to transport insulin
to the colon in a targeted manner.
Vaginal Drug Delivery
Chitosan, Gelatin, and PLGA are polymers with thioglycolic
acid added to the main amino groups. They're commonly
utilized to treat genitourinary tract mycotic infections.
Targeting by using Micro Particulate Carriers
The concept of targeting is a well-established dogma that has
recently gotten a lot of attention. The ability of a medication
to reach and engage with receptors determines its reaction.
Pellets, such as microcrystalline cellulose (MCC) and
chitosan, are typically employed, which can be manufactured
utilizing extrusion/spherization technique.
ACKNOWLEDGEMENT:
I am very thankful to Principal, Shivalik College of pharmacy,
Nangal, Punjab and my guide Dr. J.S Dua sir for their valuable
guidance. I am also thankful to my colleagues for their time
to time support.
CONCLUSION
Because of its enhanced patient enforcement and targeting
accuracy, microspheres are a safer drug administration
system than other types of drug delivery systems. Because of
its benefits of continuous and controlled-release action,
increased stability, lower dose frequency, dissolving rate,
and bioavailability, the microspheres drug delivery system is
the most commonly used drug delivery system.
Microspheres drug delivery is a safe and effective drug
delivery technique that can be utilized for a range of
applications including precision medication targeting,
floating and vaccination distribution, and more. The methods
for preparing and evaluating microspheres are widely
available and effective. Microspheres are used to imaging
malignancies, identify bimolecular interactions, and cure
cancer, among other things. As a result, microspheres will
become increasingly essential in medical research in the
future.
REFERENCES:
1. Choudhary KPR, Yarraguntla SR, Mucoadhesive microsphere for
controlled drug delivery. Biological and Pharmaceutical Bulletin
2004; 1717-24. https://doi.org/10.1248/bpb.27.1717
2. Inada A,Oue T, Yamashita, Yamasaki M Oshima T and Matsuyam H.
Development of highly water-dispersible complexes between
coenzyme Q10 and protein hydrolysates. European Journal of
Pharmaceutical Sciences. 2019; 136.
https://doi.org/10.1016/j.ejps.2019.05.014
3. Chaudhary A, Jadhav KR, Kadam VJ. An overview: Microspheres as
a nasal drug delivery system .International Journal of
Pharmaceutical Sciences Review and Research .2010Nov; 5[1].
4. Jain NK Controlled and Novel drug delivery; CBS Publishers New
Delhi, India;04 Edition .2004; 236-237,21.
Walia et al Journal of Drug Delivery & Therapeutics. 2021; 11(6):257-264
ISSN: 2250-1177 [263] CODEN (USA): JDDTAO
5. Venkatesan P,Manavalan R,Valliappan K., Microencapsulation: a
vital technique in novel drug delivery system .Journal of
Pharmaceutical Sciences and Research .2009Dec 1; 1(4):26-35.
6. Ramteke KH, Jadhav VB, Dhole SN., Microspheres;as carriers used
for novel drug delivery system. IOSR Journal of Pharmacy 2012
Jul; 2[4]:44-8. https://doi.org/10.9790/3013-24204448
7. Chein YM.Novel Drug Delivery System ,second edition ,revised
&expanded ,Marcel Dekker, Inc, New York 1992.
8. Sachan AK ,Gupta A, Arora M, Formulation &characterization of
nanostructured lipid carrier (NLC) based gel for topical delivery
of etoricoxib, Journal of drug delivery and therapeutics 2016;
6[2]:2-13. https://doi.org/10.22270/jddt.v6i2.1222
9. Vyas .SP & Khar RK Targeted and controlled drug delivery novel
carrier system, 1st edition CBS Publications and distributors,
New Delhi; 2002; 417-418.
10. Das M.K ,Ahmed A.B ,Saha D.Microsphere a drug delivery system:
A review .Int J Curr Pharma Res.2019; 11(4):34-41.
https://doi.org/10.22159/ijcpr.2019v11i4.34941
11. Rajput S, Agarwal P, Pathak A, Shrivasatava N, Baghel R.S A
review on microspheres: Method of preparation and evaluation.
World J Pharm PharmaSci.2012; 1(1):422-38.
12. Verma NK, Alam G, Vishwakarma DK, Mishra JN, KhanWU ,Singh
AP, Roshan A. Recent Advances in Microspheres Technology for
Drug Delivery. International Journal of pharmaceutical sciences
and nanotechnology .2015 May 31; 8(2):2799-813.
https://doi.org/10.37285/ijpsn.2015.8.2.2
13. Saini S, Kumar S, Choudhary M, Nitesh, Budhwar V. Microspheres
as controlled drug delivery system: An updated review. Int J
Pharma Sci Res. 2018; 9(5):1760-68.
14. Kreuter J, Nefzger M, Liehl E, Czok R, Voges R. Microspheres-A
Novel approach in Drug Delivery system .Journal of
Pharmaceutical sciences. 1983; 72:1146.
https://doi.org/10.1002/jps.2600721009
15. Singh C, Purohit S, Singh M, Pandey BL. Design and evaluation of
microspheres :A Review Journal of drug delivery research. 2013;
2(2):18-27.
16. Midha K, Nagpal M, and Arora S. Microspheres: a recent update
.International journal of Recent Scientific Research . 2015; Jul:
5859-67.
17. Sipai AB, Vandanayadav M, Mamatha Y, Prasanth VV.
Mucoadhesive Microspheres An overview. American Journal of
Pharmaceutical Research .2012; 2(1);237-58.
18. Liu G, Yang H, Zhou J, Preparation of magnetic microsphere from
water-in-oil emulsion stabilized by block copolymer dispersant,
Biomacromolecules. 2005; 6:1280-1288.
https://doi.org/10.1021/bm049316f
19. Shanthi N.C, Gupta R, Mahato K.A. Traditional and Emerging
Applications of Microspheres: A Review, International Journal of
Pharm Tech Research.2010; 2(1):675-681.
20. Najmudin M, Ahmed A, Shelar S, Patel V, Khan T. Floating
Microspheres of Ketoprofen: Formulation and Evaluation
International Journal of Pharmacy and pharmaceutical
sciences.2010; 2(2):83-87.
21. Hafeli U. Physics and chemistry Basic of Biotechnology .Focus on
biotechnology. Review .Radioactive Microspheres for Medical
Application.2002; 7:213-48. https://doi.org/10.1007/0-306-
46891-3_9
22. Yadav AV, Mote HH. Development of biodegradable starch
Microspheres for Intranasal Delivery, Indian Journal of
pharmaceutical sciences 2008; 70(2):170-174.
https://doi.org/10.4103/0250-474X.41450
23. Saralidze K, Leo H, Koole, Menno L, Knetsch W. Polymeric
Microspheres for Medical Applications,Materials.2010; 3:3357-
3564. https://doi.org/10.3390/ma3063537
24. Truvedi P, Vermal, Garud N, Preparation and Characterization of
Aclofenac Microspheres, Asian Journal of pharmaceutics 2008;
2(2):110-115. https://doi.org/10.4103/0973-8398.42498
25. Nikam VK, Gudsoorkar VR, Hiremath SN, Dolas RT, Kashid VA.
Microspheres-A Novel drug delivery system: An overview;
International Journal of pharmaceutical and chemical sciences.
2012; 1:113-128.
26. Alagusundaram M, Madhu C, Umashankari K, Attuluri B, Lavanya
C, Ramakant S. Microspheres: As novel drug delivery system
International Journal of chem. Tech Research .2009; 1(3):526-
534.
27. Sinha VR, Singla AK, Wadhawan S, Kaushik R, Kumria R, Bansal K,
Dhawan S. Chitosan microspheres as potential carrier for drugs.
International Journal of pharmaceutics .200; 274:1-33.
https://doi.org/10.1016/j.ijpharm.2003.12.026
28. Jayaprakash S, Halith S M, Mohamed Firthouse P U, Kulaturanpili
K, Abhijith, Nagarajan M. Preparation and evaluation of
biodegradable microspheres of methotrexate. Asian jounal of
pharmaceutical science. 2009; 3:26-9.
https://doi.org/10.4103/0973-8398.49171
29. Sinha V R, Bansal K, Kaushik R, Kumria R, Trehan A. Poly-
Caprolactone microspheres and nanospheres. International
journal of pharmaceutics.2004; 278 1-23.
https://doi.org/10.1016/j.ijpharm.2004.01.044
30. Kumar A, Jha S, Rawal R, Chauhan PS and Maurya SD.
Mucoadhesive microspheres for novel drug delivery system: A
review American Journal of Pharm Tech Research .2013;
3(4):197-13.
31. Gurung B.D, Kakar S. An review on microspheres. Int J Health Clin
Res.2020; 3(1):11-24.
32. Meena KP, Dangi JS, Samal PK, Namedo KP. Recent advances in
microspheres manufacturing technology .International Journal
of pharmacy and technology .2011; 3(1);854-855.
33. Kadam NR, Suvarna V. Microspheres: A Brief review .Asian
Journal of Biomedical and Pharmaceutical Sciences.2015 Aug 1;
5(47) :13. https://doi.org/10.15272/ajbps.v5i47.713
34. Thanoo BC, Sunny M, Jayakrishanan A. Cross-linked chitosan
microspheres. Preparation and evaluation as a matrix for the
controlled release of pharmaceuticals. Journal of pharmacy and
pharmacology.1992; 44:283-286.
https://doi.org/10.1111/j.2042-7158.1992.tb03607.x
35. Parmar H, Bakliwal S, Gujarathi N, Rane B, Pawar S. Different
method of formulation and evaluation of mucoadhesive
microspheres. International Journal of Applied Biology and
pharmaceutical technology .2010; 1(3):1157-1167.
36. Moy AC, Mathew ST, Mattapan R, Prasanth VV. Microspheres -An
Overview .International journal of Pharmaceutical and
Biomedical Sciences .2011; 2(2):332-338.
37. Alagusundaram M, Chetty MSC, Umashankari K, Badarinath AV,
Lavanya C, Ramakant S. Microspheres as a novel drug delivery
system-A review. International Journal of chem. Tech Research
.2009; 1:526-34.
38. Singh K, Purohit S, Singh M, Pandey B.L. Design and evaluation of
microspheres: A review, Journal of drug development and
research 2013; 2(2):18-27.
39. Sahil K, Akanksha M, Premjeet S, Bilandi A, Kapoor B.
Microsphere: A review. International journal of research in
pharmacy and chemistry 2011; 1(11):84-98.
40. Pavan K. B, Chandiran I.S , Bhavya B, Sindhuri M. Micropaticulate
drug delivery system: A review .Indian journal of
pharmaceutical science& research .2011; 1(1):19-37.
41. Dhakar R.C, Maurya S.D, Sagar B.P.S, Bhagat S, Prajapati S.K, Jain
C.P. Variables influencing the drug entrapment efficiency of
microspheres: A Pharmaceutical review .Der Pharacia
Lettre.2010; 2(5):102-116.
42. Gogu P.K Preparation &invivo characterization of spray dried
microspheres formulations encapsulating 4-chlorocurcumin.
Walia et al Journal of Drug Delivery & Therapeutics. 2021; 11(6):257-264
ISSN: 2250-1177 [264] CODEN (USA): JDDTAO
Indian Journal of pharmaceutical sciences.2010; 72:346-352.
https://doi.org/10.4103/0250-474X.70481
43. Alagusundram M, Chetty MS, Umashankari K, Badarinath AV,
Lavanya C, Ramkanth S. Microspheres as a novel drug delivery
system: A review .International Journal of Chem. Tech Research
2009; 1(3):526-534.
44. Patel NR, Patel DA, Bharadia PD, Pandya V, Modi V. Microspheres
as a novel drug delivery .International Journal of pharmacy &life
sciences. 2011; 2(8). https://doi.org/10.4103/0975-
8453.86290
45. Thadanki M, Chadalawada PK, Lavanya P, Umashankar
D:Formulation and evaluation of sustained release saxagliptin
microspheres by ionotropic gelation method. International
Journal of bioassays. International journal of bioassays . 2017;
pgno.5328-5333. https://doi.org/10.21746/ijbio.2017.03.0010
46. Dupinder K, Saini S:Variable Effecting Drug Entrapment
Efficiency of microspheres :A review, International Research
Journal of pharmaceutical and applied Science (IRJPAS); 2013;
3(3):24-28.
47. Sailaja A, Anusha K. Review on microspheres as a drug delivery
carrier. International journal of Advances in pharmaceutics
2017; 06(05):96-102.
48. Tarun V, Gupta J. Pharmaceutical Applications of microspheres:
An approach for the treatment of various diseases; International
journal of pharmaceutical sciences and research, 2017;
8(1):3257-3259.
49. Sharma N, Purwar N, and Gupta PC. Microspheres as drug
carriers for controlled drug delivery. A Review .International
Journal of pharmaceutical sciences and research 6(11):4579-87
