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Human Journals
Review Article
May 2022 Vol.:24, Issue:2
© All rights are reserved by Ishwar Singh et al.
Microspheres: A Novel Drug Delivery System
www.ijppr.humanjournals.com
Keywords: characteristics, advantages, types, preparation
techniques, evaluation parameter, and applications of
microspheres
ABSTRACT
Microspheres are the micro-particulate form of drug
delivery. Microspheres as drug carriers are one of the most
cutting-edge ways to maintain and control pharmacological
action in a specific region. Microspheres are microscopic
particles in the range of (1-1000 micro-meters).
Microspheres provide temporary embolization. These are
excreted from the body by natural metabolic functioning
after completing their clinical goal without interfering with
the function of other organs. Microspheres are prepared
with natural and synthetic polymers. There are different
types of techniques used for the preparation of
microspheres like single emulsion technique, double
emulsion technique, polymerization, phase separation,
spray drying, solvent extraction, and emulsion solvent
evaporation is some of the techniques used to make
microspheres. Microspheres will play a key role in
innovative medicine delivery in the future.
Bharat Sharma, * Ishwar Singh, Jatin Sharma,
Amit Chaudhary, Inder Kumar
School of Pharmacy, Abhilashi University, Chailchowk,
Mandi, HP, India.
Submitted: 21 April 2022
Accepted: 27 April 2022
Published: 30 May 2022
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48
INTRODUCTION
Compared to traditional multi-dose therapy, novel drug delivery systems have many
advantages. Micro particulate drug delivery systems, according to recent trends, are
particularly well suited to achieving controlled release and delayed-release oral formulations
with low risk of dose dumping, blending flexibility to achieve different release patterns and
reproducible and short gastric residence time. (1) Drug delivery methods have improved,
particularly those that give a prolonged and controlled action of the drug to the desired effect
region. These innovative drug delivery systems can change the rate at which drugs are
administered, prolong the therapeutic effect, and/or deliver drugs to a specific location. (2)
Microspheres as drug carriers are one of the most cutting-edge methods for sustaining and
controlling pharmacological action in a specific location. Microspheres made of degradable
materials are used to provide transient embolization. They should, in theory, be expelled from
the body once they have achieved their clinical aim without interfering with the operation of
other organs. (3) Particulate delivery systems have attracted a lot of attention in the
pharmaceutical industry because they can modulate and target the release of active
ingredients. Which, in theory, should allow for drug release to be modulated in response to
therapeutic needs.(4) Pre-programmed drug release profiles that meet the therapeutic needs of
the patient can be offered. This article provides an overview of the most important past,
current, and future initiatives for improving the efficiency of various medical treatments by
employing drug-loaded microparticles.(5) Microparticles bind and fuse with their target cells
via receptor-ligand interactions, acting as biological vectors that mediate vascular
inflammation and coagulation. Micro particles have thus been shown to have an important
role in a number of cardiovascular illnesses. A growing amount of evidence suggests that the
inflammatory and pro-coagulant effects of micro particles on their target cells are caused by a
unique lipid content as well as the transfer of inflammatory cell components from their source
cells.(6) Microparticles are effective for drug delivery, however, they have a low site-
specificity and are removed quickly by the reticuloendothelial system in normal
circumstances. (7) Membrane vesicles have sparked a surge of interest in several domains of
biology, including vascular biology and thrombosis, over the last ten years. To define
submicron membrane vesicles ejected by active or dying cells, the term cell dust has been
substituted by the term microparticles. (8) The pharmaceutical industry is used to create
microspheres. The stability of carriers is determined by microspheres of various
microstructures. The microsphere is crucial in increasing the drug's bioavailability. It's the
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ability to combine a drug's concentration in a concentrated form. (9) Because of the spheres'
form and size, they have a high surface area to volume ratio, which aids cell adhesion,
proliferation, and differentiation.(10)
Microspheres are microscopic spherical particles (usually 1 to 1000 micrometers).
Microspheres are also known as microparticles or micro-particles. Microspheres can be made
of both natural and man-made materials. Because microspheres are biocompatible but not
biodegradable, no biological waste is produced. (11) Protein entrapment in biodegradable
microspheres has received a lot of attention as a way to make protein formulations with a
longer release time. (12) Because of their superior biocompatibility, non-therapeutically
active proteins, and peptides, PBT multi-block copolymers have a lot of potential as matrices
consisting of poly (lactase-co-glycoside) matrix material for a controlled release system for
(PLG). Characteristics of toxicity and biodegradation.(13)
Fig. 1: Microspheres as a group (14)
Microspheres are a key component of novel drug delivery systems. Microspheres are free-
flowing powders comprised of biodegradable proteins or synthetic polymers with particle
sizes of less than 200 micrometers. Microspheres reduce dosage frequency and improve
patient compliance by developing and evaluating Sustained Release microspheres for
effective diabetes control. A controlled release approach is intended to extend the time it
spends in the stomach by interacting with the mucosa. (15) Microsphere carrier systems are
made by using various polymers and prepared with different techniques.(16) The drug is
placed on the microsphere's surface or inside it, and it is released as the matrix components
disintegrate. Before they are released, peptides and proteins can be safeguarded. The most
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significant disadvantage of microspheres is that they must be injected subcutaneously, which
causes pain and may result in patient noncompliance. (17)
Ideal Characteristics of Microspheres:
• Ability to control the release rate for a predefined period.
• Higher concentrations of the drug can be given to serve as a depot. (18)
• Non-toxic.
• Relative stability.
• Bioresorbability.
• Increase therapeutic efficiency.
• Control of content release.
• Stability of the preparation after synthesis with a clinically acceptable shelf life.
• Biocompatibility with controllable biodegradability.
• Controlled particle size and dispersion of the drug in aqueous solvent for parenteral. (19)
• Longer duration of action.
• Protect drug.
• Serializability.
• Water solubility or dispersibility. (20)
Advantages of Microspheres:
• Increase the gastric residence time of dosage forms.
• Size reduction leads to an increase in surface area which can enhance the solubility of the
poorly soluble drug.
• Provide constant drug concentration in the blood which can increase patent compliance,
• Decrease dose and toxicity. (21)
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• Coating of drug with polymers helps the drug from enzymatic cleavage hence found to be
best for drug delivery.
• It should satisfy the particle size requirement. The drug should not be adversely affected
by the method of preparation. (22)
• Less dosing frequency leads to better patient compliance.
• Better drug utilization will improve the bioavailability and reduce the incidence or
intensity of adverse effects. (23)
• Protects the GIT from irritant effects of the drug.
• Convert liquid to solid form and mask the bitter taste.
• Reliable means to deliver the drug to the target site with specificity, if modified, and to
maintain the desired concentration at the site of interest without untoward effects. (24)
• Reduce the reactivity of the core concerning the outside environment.
• Biodegradable microspheres have the advantage over large polymer implants in that they
do not require surgical procedures for implantation and removal.
• Controlled release delivery biodegradable microspheres are used to control drug release
rates thereby decreasing toxic side effects, and eliminating the inconvenience of repeated
injections 10. (25)
• Microspheres provide a constant and prolonged therapeutic effect.
• Reduces the dosing frequency and thereby improves patient compliance.
• They could be injected into the body due to their spherical shape and smaller size. (26)
• Better drug utilization will improve the bioavailability and reduce the incidence or
intensity of adverse effects. (27)
Limitation
• The modified release from the formulations.
• The release rate of the controlled release dosage form may vary from a variety of factors
like food and the rate of transit through the gut. (28)
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• Differences in the release rate from one dose to another.
• Controlled release formulations generally contain a higher drug load and thus any loss of
integrity of the release characteristics of the dosage form may lead to potential toxicity.
• Dosage forms of this kind should not be crushed or chewed. (29)
TYPES OF MICROSPHERES
1. Bio-adhesive microspheres: Adhesion is defined as the adhesion of a medication to a
membrane by the use of water-soluble polymers' adhesive properties. Bio adhesion is defined
as the attachment of a medication delivery device to a mucosal membrane, such as the buccal,
ocular, rectal, or nasal mucosa. These microspheres have a longer residence duration at the
application site, resulting in closer contact with the absorption site and improved therapeutic
effect. (30)
2. Magnetic Microspheres: This type of delivery mechanism is critical because it allows
the drug to be delivered to the illness location. A higher amount of freely circulating
medicine can be substituted with a smaller amount of magnetically focused drug in this
situation. Magnetic carriers receive magnetic responses to a magnetic field from integrated
components such as chitosan, dextran, and other materials utilized in magnetic microspheres.
Therapeutic magnetic microspheres and diagnostic magnetic microspheres are the two types.
(31)
3. Floating Microspheres: Floating kinds of gastro-retentive medication administration
have the benefit of having a lower bulk density than gastric fluid and thus remaining buoyant
in the stomach without influencing gastric emptying pace. The medicine is slowly released at
the desired rate, and the system is discovered to be floating on gastric content, which
increases stomach residence and increases plasma concentration fluctuation. It also
minimizes the likelihood of dosage dumping. It has a longer-lasting therapeutic impact and
hence reduces dose frequency. Depending on the pharmacokinetic features of medicine, such
as Famotidine, it may be given in the form of floating microspheres. (32)
4. Radioactive Microspheres: Microspheres deliver a high dosage of radiation to the
targeted locations while causing no harm to the surrounding tissues. Microspheres do not
manufacture radioactivity; instead, they work from a standard distance inside a radioisotope,
and the different types of radioactive microspheres are emitters, emitters, and emitters. (33)
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5. Diagnostic microspheres: The magnetic drug transport method is based on the fact that
the drug can be encapsulated within the magnetic microsphere or conjugated on the
microsphere's surface. The carrier's build-up at the target site allows them to distribute the
medicine locally. (34)
6. Polymeric microspheres: Biodegradable polymeric microspheres and Synthetic
polymeric microspheres are the two types of polymeric microspheres.
i) Biodegradable polymeric microspheres: Natural polymers like starch are used because
they are biodegradable, biocompatible, and bio sticky. Due to its high degree of swelling
property with an aqueous medium, biodegradable polymers lengthen the residence period
when in contact with mucous membranes, resulting in gel formation. The rate and amount of
medication release are controlled by the polymer concentration and the release pattern
throughout time. The fundamental disadvantage is that the drug loading efficiency of
biodegradable microspheres in clinical application is complex, making drug release difficult
to control. They do, however, have a broad range of applications in microsphere-based
treatment.
ii) Synthetic polymeric microspheres: The interest of synthetic polymeric microspheres
are widely used in clinical applications. Moreover, that also used as bulking agent, fillers,
embolic particles, drug delivery vehicles etc. and proved to be safe and biocompatible. But
the main disadvantage of these kinds of microspheres, are tend to migrate away from the
injection site and lead to potential risk, embolism and further organ damage.(35)
MATERIALS USED IN THE PREPARATION OF THE MICROSPHERE
Microspheres used usually are polymers. They are classified into two types:
i) Natural polymers
ii) Synthetic Polymers
i) Natural polymers
Natural polymers are obtained from different sources like carbohydrates proteins and
chemically modified Carbohydrates. Carbohydrates: Agarose, Carrageenan, Chitosan, and
Starch Proteins: Albumin, Collagen, and gelatin chemically modified carbohydrates: Poly
dextran, Poly starch.
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Microspheres should satisfy certain criteria as follows:
• The medicine should be present in rather high amounts. Stability of the preparation after
synthesis with acceptable shelf life.
• Compatibility with biodegradability that can be controlled.
• Chemical alteration is a possibility.
• Particle size and solubility in aqueous injection vehicles are controlled.
• Controlled release of the active pharmaceutical reagent over a long period.
ii) Synthetic polymers
Synthetic polymers are divided into two types:
• Biodegradable polymers E.g., Lactides, Glycolides & their co-polymers, Poly anhydrides,
Poly alkyl cyanoacrylates
• Non-biodegradable polymers E.g., Polymethylmethacrylate, Glycidyl methacrylate,
Acrolein, and Epoxy polymers.
Ophthalmic, oral, and parenteral preparations could all benefit from poly alkyl cyanoacrylates
as a drug carrier. Polylactic acid is an effective carrier for anticancer drugs such as cisplatin,
cyclophosphamide, and doxorubicin, as well as narcotic antagonists. For the anti-malarial
drug's sustained-release preparation, a copolymer of polylactic acid and polyglycolic acid is
employed. The ocular administration of timolol maleate is encapsulated in poly adipic
anhydride. Microspheres made of poly acrolein are a useful variety. (36)
DRUG LOADING TECHNIQUES IN MICROSPHERES
The medications are loaded into the microspheres in one of two ways:
i) During the microsphere preparation
ii) After the microsphere preparation, by incubating them with the drug solution.
Active components can be loaded in a variety of ways, including physical trapping, chemical
coupling, and surface absorption. The presence of additives, the method of preparation, the
heat of polymerization, and the intensity of agitation, among other process variables, were
discovered to result in the highest drug loading in microspheres when the drug was
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incorporated during the preparation process. However, this can be influenced by a variety of
other process variables such as the presence of additives, the method of preparation, the heat
of polymerization, and the intensity of agitation, among others. Drug loading can be achieved
after the microspheres have been prepared by incubating them in a suitable solvent containing
a high concentration of the drug. Drugs can be put into microspheres through absorption as
well as penetration or diffusion through the holes of the microspheres. (37)
Fig. 2: Mix Microspheres with Insulin (38)
METHOD OF PREPARATION
These methods can help with a variety of issues that arise during the creation of a
pharmaceutical dosage form. Even though there are a lot of challenges to overcome to
accomplish prolonged gastric retention, a big number of companies are working to
commercialize this technology. (39) The microspheres were washed in petroleum ether
several times until they were oil-free. (40) Before being stored in desiccators over fused
calcium chloride, the microspheres were collected and dried for one hour at room
temperature. (41)
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• Single emulsion technique
• Double emulsion technique
• Polymerization
i) Normal polymerization
ii) Interfacial polymerization
• Phase separation/ Coacervation
• Spray drying
• Solvent extraction
• Emulsion Solvent Evaporation
• Single emulsion technique:
The single emulsion technique is used to create microparticulate carriers for natural
polymers, such as proteins and carbohydrates. Natural polymers are first dissolved/dispersed
in aqueous media, then dispersed in a non-aqueous liquid, such as oil. Cross-linking of
scattered globules is performed in the second step of the process. Heat or chemical cross-
linking agents such as glutaraldehyde, formaldehyde, diacid chloride, and others can be used
to cross-link the molecules. (42)
Fig.3 Single emulsion technique (43)
• Double Emulsion Technique:
This approach is suitable for water-soluble medicines, peptides, proteins, and vaccines and
can be utilized with both natural and manufactured polymers. The preparation of
microspheres with this method necessitates the creation of several emulsions. The aqueous
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protein solution is disseminated in a lipophilic organic continuous phase, which contains the
active ingredients, in this approach. A polymer solution encapsulates protein distributed in
the aqueous phase in the continuous phase. After that, the primary emulsion is homogenized
before being added to a PVA aqueous solution (Poly Vinyl Alcohol). The emulsion is
subsequently subjected to solvent removal, either by solvent evaporation or solvent
extraction. (44)
Fig. 4: Double Emulsion Technique (45)
• Polymerization Techniques: The different types of polymeric microspheres can be
classified as follows:
i) Normal Polymerization Bulk polymerization involves heating a monomer or a mixture
of monomers with an initiator or catalyst to commence polymerization. The resulting
polymer can be molded into microspheres. Drug loading can be accomplished by medicating
the polymerization process. It is a method for forming pure polymers, but it is extremely
difficult to eliminate the heat of the response from damaging active thermolabile components.
Pearl polymerization is a type of suspension polymerization that takes place at a lower
temperature and involves heating a monomer combination with an active component such as
droplet dispersion in a continuous aqueous phase. The suspension method is used to create
microspheres with a diameter of less than 100um.
ii) Interfacial Polymerization A polymer film envelops the dispersed phase, which is
generated by the interaction of different monomers between two immiscible liquid phases.
The two monomers react in this process; one is dissolved in continuous phases, while the
other is dispersed in an aqueous natured continuous phase, where the second monomer is
emulsified.(46)
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Fig.5: Interfacial Polymerization (47)
• Phase separation/ Coacervation: This method divides macromolecular fluid into two
immiscible layers: a thick coacervate layer, which is relatively dense in macromolecules, and
a distilled layer of equilibrium. When only one macromolecule is present, this approach is
called basic coacervation. Complex coacervation is defined as the interaction of two or more
opposite-charge macromolecules. Specific circumstances, such as temperature changes,
trigger the former. Because non-solvent or micro-ions increase connections between polymer
and polymer through polymer-solvent interactions, they contribute to dehydration in
macromolecules. Different qualities in the microsphere can be created using this method.(48)
Fig. 6: Phase separation/ Coacervation (49)
• Spray Drying: The polymer is first dissolved in a suitably volatile organic solvent such
as dichloromethane, acetone, etc. before being spray dried. Under high-speed
homogenization, the solid drug is disseminated in the polymer solution. A stream of hot air is
used to atomize the dispersion. The atomization process produces small droplets or fine mists
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from which the solvent evaporates quickly, resulting in the creation of microspheres with
sizes ranging from 1 to 100 micrometers. The cyclone separator separates the microparticles
from the heated air, while vacuum drying removes any trace of solvent. One of the most
significant benefits of the process is its ability to operate under aseptic circumstances. The
procedure is very quick, resulting in the creation of porous microparticles.(50)
Fig. 7: Spray drying technique (51)
• Solvent extraction: The extraction of solvents is often done in two steps. To make an
emulsion with the required droplet size, the drug/matrix dispersion is first combined with a
tiny amount of continuous phase (distribution). Then, at a concentration adequate to absorb
the whole solvent leaching from the solidifying microspheres, a new continuous phase and/or
further extraction agents are added. Despite this, a patent application describes a one-step
solvent extraction method. The drug/ matrix dispersion is promptly homogenized with such a
quantity of continuous phase that it is capable of dissolving the complete amount of the
disperse phase solvent at once, without any preliminary emulsification procedure. However,
to produce homogeneously distributed particles, this procedure necessitates careful setting of
the physicochemical parameters during the homogenization step.(52)
Fig. 8: Solvent extraction (53)
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• Emulsion solvent evaporation: The polymer is first dissolved in acetone, then the
medication is added to the polymer solution, followed by the addition of magnesium stearate.
The dispersion was then added to a liquid paraffin mixture while being stirred with a
mechanical stirrer. Until the acetone had evaporated, the stirring was continued. The resulting
microspheres are filtered and washed. (54)
Fig. 9: Emulsion solvent evaporation(55)
EVALUATION PARAMETER
• Floating behavior
• Molecular size and shape
• Density determination
• Angle of contact
• Encapsulation Efficiency
• Electron spectroscopy for chemical analysis
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• Fourier transform-infrared spectroscopy
• In-Vitro Methods
• In-vitro drug release study
Floating behavior
When floating microspheres are distributed in simulated stomach juice without enzymes, the
polymer dissolves into solution, causing pores to form on the microspheres due to matrix
erosion. As a result of this, the microspheres float. The following equation was used to
calculate the proportion of the floating microsphere:(56)
Molecular size and shape
Light microscopy or scanning electron microscopy can be used to determine the size, shape,
and external structure of microspheres. (57)
Density determination
A multi-volume pycnometer is used to measure the thickness of the microspheres. According
to the example, something is set in the multi-volume pycnometer in a cup. The chamber is
filled with helium at a constant weight to allow for an extension.(58) Within the gathering,
the weight of the outcomes is diminished as a result of this evolution. The introduction
weight is determined when the proportion between two consecutive weight readings
decreases. Based on two weight readings, the volume may determine the thickness of the
microspheres transporter.(59)
Angle of contact
The angle of contact is used to determine a micro particle channel's wetting property. The
inclination of microspheres is described by the term hydrophobicity, which is also known as
hydrophilicity.(60) The point of contact between the strong/air/water interfaces must be
determined. The progressing and receding point of contact can be determined by adding a
bead to a roundabout cell mounted over the aim of an increased magnifying device. In a
microsphere affidavit moment, the contact points are approximated at 20°C.(61)
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Encapsulation Efficiency
Lysate can determine the microspheres' catchability or percent capture by allowing them to
be washed. The lysate is then subjected to dynamic component assurance, as indicated by the
monograph. Encapsulation efficiency is calculated using the following equation:(62)
Electron spectroscopy for chemical analysis
The microsphere's surface science necessitates the employment of electron spectroscopy for
substance investigation (ESCA). The use of electron spectroscopy for compound assessment
allows for the nuclear organization of these stocks' surfaces (ESCA).(63) The spectra are used
to check that the surface of the biodegradable microsphere is clean. These spectra were
created with ECSA. (64)
Fourier transform-infrared spectroscopy
The FTIR is utilized to determine the corruption of the transporter framework's polymeric
lattice. Using rotated full reflectance, the studied surface of the microspheres is estimated
(ATR). To get IR spectra of surface material, the IR bar is passed from the ATR cell and
reflected broadly throughout the example.(65) The surface arrangement of the microspheres,
which is defined by the assembly procedures and conditions, is used to generate the ATR-
FTIR data. (66)
In vivo release
In addition to release behavior, the in vivo examination considers biocompatibility, excessive
toxicity, and inflammatory response. Tissue reactions in vivo are often separated into three
stages:
i) local inflammation
ii) When microspheres degenerate to a particular size, a thin fiber wall forms at the interface
between them and the organization, and phagocytosis occurs.(67)
In-vitro drug release study
The In-Vitro Techniques approach is a method for determining the delivery properties and
penetrability of a medicament. Because of the numerous in-vivo and in-vitro techniques used,
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this is the case. Quality control procedures are employed in the manufacture of
pharmaceuticals and the development of new goods.(68) In vitro testing of drug discharge
Characterize conditions are crucial when delicate and reproducible information is collected
from physic synthetically and hydrodynamically. This mechanical assembly used multiple
specialists for shifting plans and under changing conditions; these conditions vary depending
on the application and stage of the measurement structure improvement.(69)
Microspheres in Advanced Healthcare Applications
• Microspheres are small spherical particles with a diameter of 1–1000 m that are usually
free-flowing and can be made of synthetic or natural materials. Because multiple methods
exist to make them with great control over size, shape, and surface morphology, as well as
solid, porous, or capsular internal structures, they have found significant usage in healthcare
applications. This gives the microsphere the capacity to encapsulate practically any desired
molecule and modulate its release, making it a popular structure for medication delivery
systems.
• Magnetic microspheres can be made vulnerable to magnetic fields and used in cell
isolation, protein purification, and medication targeting. Low-density systems, such as gastro-
retentive floating microspheres that allow for extended drug release in the stomach, maybe
chosen for use in oral medication formulations.
• Polymeric microspheres have been widely utilized to deliver peptides, proteins,
hormones, and vaccines, with the polymer matrix frequently being regulated through
biodegradation.(70)
• Cancer research
• Controlled-Release Vaccines
• DNA Encapsulation
• Ophthalmic Drug Delivery
• Gene delivery
• Intra tumoral and local drug delivery
• Oral drug delivery
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• Nasal drug delivery
• Buccal drug delivery
• Gastrointestinal drug delivery
• Peroral drug delivery
• Transdermal drug delivery
• Colonic drug delivery
• Diagnostic uses of radioactive microspheres:
Deep vein thrombosis thrombus imaging Measurement of blood flow, imaging of the liver
and spleen, imaging of the bone marrow, and imaging of tumours.(71)
CONCLUSION
In the micrometre scale, a microsphere is a small spherical entity with sizes ranging from
1mm to 1000mm. Microspheres are typically free-flowing powders made up of naturally
biodegradable proteins or synthetic polymers with a particle size of less than 200
micrometers. There are several methods for delivering a medicinal medicine to the target site
in a prolonged controlled release manner. One such technique is to use microspheres as
medication carriers. Oral, targeted, sustained, topical, and different biotechnology
applications such as gene therapy, for example, are all possibilities. By enhancing safety and
minimizing toxicity, innovative delivery systems can provide substantially more therapeutic
and commercial benefits. Microspheres will play a central and significant role in novel drug
delivery in the future, particularly in diseased cell sorting, diagnostics, gene & genetic
materials, safe, targeted, specific, and effective in-vitro delivery, and supplements as
miniature versions of diseased organs and tissues in the body, thanks to the combination of
various other strategies.
CONFLICT OF INTEREST
None
REFERENCES
1. Poovi Ganesan, Arul Jasmine Deepa Johnson LS and AD. Review on microsphere. Am J drug Discov Dev.
2014;4(3):1–28.
2. Vaibhav R, Satya SS, Roop S, Lal N, Pragya Y. Review Article Microspheres : a Promising Drug Carrier. J
www.ijppr.humanjournals.com
Citation: Ishwar Singh et al. Ijppr.Human, 2022; Vol. 24 (2): 47-67.
65
Drug Deliv Ther. 2016;6:18–26.
3. Doucet J, Kiri L, Connell KO, Kehoe S, Lewandowski RJ, Liu DM, et al. Advances in degradable embolic
microspheres : A state of the art review. J Funct Biomater Rev. 2018;9(14):1–24.
4. Scalia S, Young PM, Traini D. Solid lipid microparticles as an approach to drug delivery. Expert Opin Drug
Deliv. 2014;12(5):1–17.
5. Juergen Siepmann FS. Microparticles used as drug delivery systems. Progr Colloid Polym Sci.
2006;133:15–21.
6. Diehl P, Fricke A, Sander L, Stamm J, Bassler N, Htun N, et al. Microparticles : Major transport vehicles
for distinct micro RNAs in circulation. Cardiovasc Res. 2012;93(4):633–44.
7. Momoh MA, Kenechukwu FC, Attama AA. Formulation and evaluation of novel solid lipid microparticles
as a sustained release system for the delivery of metformin hydrochloride. Inf Healthc. 2013;20(3):102–11.
8. Boulanger CM, Dignat-George F, Boulanger CM. Microparticles : An introduction. Arter Thromb Vasc
Biol. 2011;31(1):2–3.
9. R. D. Salunke*, M. T. Deshmukh, R. V. Shete RSS, Department. Microspheres: A review. Curr Pharma
Res. 2019;9(2):2230–7842.
10. Wee CY, Yang Z, Thian ES. Past , present and future development of microspheres for bone tissue
regeneration : a review. Mater Technol. 2020;36(6):1–11.
11. Alam S, Hasan K, Neaz S, Hussain N, Hossain F. Diabetes mellitus : Insights from epidemiology ,
biochemistry , risk factors , diagnosis , complications and comprehensive management. Diabetology.
2021;2(2):36–50.
12. Ta.S. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37(1):81–90.
13. Ohiagu FO, Chikezie PC, Chikezie CM. Pathophysiology of diabetes mellitus complications: Metabolic
events and control. Biomed Res Ther. 2021;8(3):4243–57.
14. Lee J, Ha JU, Choe S, Lee CS, Shim SE. Synthesis of highly monodisperse polystyrene microspheres via
dispersion polymerization using an amphoteric initiator. J Colloid Interface Sci. 2006;298(2):663–71.
15. Rathore B, Yadav A, Nayak G, Saraogi GK, Singhai AK. A review on microspheres as drug delivery
carriers for management of diabetes mellitus. Int J Pharm Life Sci. 2012;3(10):2064–70.
16. Arshady R. Microspheres for biomedical applications: preparation of reactive and labelled microspheres.
Biomaterials. 1993;14(1):5–15.
17. Cai Y, Wei L, Ma L, Huang X, Tao A, Liu Z, et al. Long-acting preparations of exenatide. Drug Des Devel
Ther. 2013;7:963–70.
18. Lee DW, Hwang SJ, Park JB, Park HJ. Preparation and release characteristics of polymer-coated and
blended alginate microspheres. J Microencapsul. 2003;20(2):179–92.
19. Li X, Wei Y, Lv P, Wu Y, Ogino K, Ma G. Preparation of ropivacaine loaded PLGA microspheres as
controlled-release system with narrow size distribution and high loading efficiency. Colloids Surfaces A
Physicochem Eng Asp. 2019;562:237–46.
20. Wang X, Wang X, Liu L, Bai L, An H, Zheng L, et al. Preparation and characterization of carbon aerogel
microspheres by an inverse emulsion polymerization. J Non Cryst Solids. 2011;357(3):793–7.
21. Yang Z, Peng H, Wang W, Liu T. Crystallization behavior of poly(ε-caprolactone)/layered double
hydroxide nanocomposites. J Appl Polym Sci. 2010;116(5):2658–67.
22. Katz LC, Iarovici DM. Green fluorescent latex microspheres: A new retrograde tracer. Neuroscience.
1990;34(2):511–20.
23. Patil S, Sawant K. Mucoadhesive microspheres: A promising tool in Drug Delivery. Curr Drug Deliv.
2008;5(4):312–8.
24. Darafsheh A, Limberopoulos NI, Derov JS, Walker DE, Astratov VN. Advantages of microsphere-assisted
super-resolution imaging technique over solid immersion lens and confocal microscopies. Appl Phys Lett.
2014;104(6):1–5.
25. Virmani T, Gupta J. Pharmaceutical application of microspheres: An approach for the treatment of various
diseases. Int J Pharm Sci Res. 2017;8(8):3252–60.
26. Ré MI, Biscans B. Preparation of microspheres of ketoprofen with acrylic polymers by a quasi-emulsion
solvent diffusion method. Powder Technol. 1999;101(2):120–33.
27. Kshirsagar DS, Saudagar RB. Microsphere: A review. Int J Res Pharm Chem. 2011;1(4):1184–98.
www.ijppr.humanjournals.com
Citation: Ishwar Singh et al. Ijppr.Human, 2022; Vol. 24 (2): 47-67.
66
28. Martins KF, Messias AD, Leite FL, Duek EAR. Preparation and characterization of paclitaxel-loaded
PLDLA microspheres. Mater Res. 2014;17(3):650–6.
29. Yang X, Flynn R, Von Der Kammer F, Hofmann T. Influence of ionic strength and pH on the limitation of
latex microsphere deposition sites on iron-oxide coated sand by humic acid. Environ Pollut. 2011;159(7):1896–
904.
30. C. Singh; S. Purohit; M. Singh; B. L. Pandey. Design and evaluation of microspheres : A review. J Drug
Deliv Res. 2013;2(2):18–27.
31. Prasad BSG, Gupta VRM, Devanna N, Jayasurya K. Microspheres as drug delivery system – A review. J
Glob Trends Pharm Sci. 2014;5(3):1961–72.
32. Virmani T, Gupta J. Pharmaceutical application of microspheres: An approach for the treatment of various
diseases. IJPSR. 2017;8(8):3252–60.
33. Birajdar AA, Deshmukh MT, Shete R V. A review on gastro - retentive floating microspheres. J Drug Deliv
Ther. 2021;11(1):131–8.
34. Nv P, Nv W, Ss T, Sudarshan US. Microspheres : A Novel Drug Delivery System. Am J PharmTech Res.
2020;10(2):286–301.
35. K AKS and A. Review on microspheres as a drug delivery carrier. Int J Adv Pharm. 2017;6(5):96–102.
36. Raj H, Sharma S, Sharma A, Verma KK, Chaudhary A. Journal of drug delivery and therapeutics A Novel
Drug Delivery System : Review on Microspheres. J Drug Deliv Ther Open. 2021;11(2):156–61.
37. Kumari N, Aggarwal G, Harikumar SL. Mucoadhesive microspheres: A review. J Drug Deliv Ther.
2014;4(5):48–54.
38. He P, Tang Z, Lin L, Deng M, Pang X, Zhuang X, et al. Novel biodegradable and pH-sensitive poly(ester
amide) microspheres for oral insulin delivery. Macromol Biosci. 2012;12(4):547–56.
39. Megha Sharma*1 and Seema Kohali. Floating drug delivery of antidiabetic drugs: An overview. Int J
Pharma Bio Sci. 2015;6(3):679–85.
40. Garud N, Garud A. Preparation and in-vitro evaluation of metformin microspheres using non-aqueous
solvent evaporation technique. Trop J Pharm Res. 2012;11(4):577–83.
41. Huang HP, Ghebre-Sellassie I. Preparation of microspheres of water-soluble pharmaceuticals. J
Microencapsul. 1989;6(2):219–25.
42. Bellah SF, Ullah S, Harris KK. IOSR Journal of Pharmacy paper , research paper publishing , where to
publish ... IOSR J Pharm. 2012;6(3):44–8.
43. Article R. Microparticulate drug delivery system- A review. World J Pharm Life Sci. 2016;2(6):243–58.
44. Sharma N. Microspheres as drug carriers for controlled drug delivery: A review. Int J Pharm Sci Res.
2015;6(11):2320–5148.
45. Prashant S, Prakash D, Ramesh B, Singh N, Mani TT. Biodegradable polymeric microspheres as drug
carriers: A review. Indian J Nov Drug Deliv. 2011;3(2):70–82.
46. Rajan1* VR and J. A comprehensive review of microspheres and its uses in cancer treatment. World J
Pharm Res. 2021;10(5):879–900.
47. Cheng XQ, Zhang YL, Wang ZX, Guo ZH, Bai YP, Shao L. Recent advances in polymeric solvent-resistant
nanofiltration membranes. Adv Polym Technol. 2014;33(1):1–24.
48. Dhadde G, Raut ID. A review on microspheres : Types , method of preparation , characterization and
application. Asian J Pharm Technol. 2021;11(2):1–7.
49. Dattatraya V. Microsphere: A novel drug delivery system. IJPT. 2012;4(1):4060–6.
50. Sahil K, Akanksha M, Premjeet S, Bilandi A, Kapoor B. Microsphere : A review. Int J Res Pharm Chem.
2015;1(4):2231–781.
51. Li X, Zhou J, Wang J, Qiao W, Ling L, Long D. Large-scale synthesis of mesoporous carbon microspheres
with controllable structure and nitrogen doping using a spray drying method. RSC Adv. 2014;4(107):62662–5.
52. Freitas S, Merkle HP, Gander B. Microencapsulation by solvent extraction / evaporation : reviewing the
state of the art of microsphere preparation process technology. J Control Release. 2005;102(2):313–32.
53. Széliga ME, Nacucchio MC. Comparison of microencapsulation by emulsion-solvent extraction/
evaporation technique using derivatives cellulose and acrylate- methacrylate copolymer as carriers. Jundishapur
J Nat Pharm Prod. 2015;17(1–2):81–9.
54. Mishra S, Sharm D, Chaturvedi V, Yadav S. Recent advancement microsphere of drug delivery through. Int
www.ijppr.humanjournals.com
Citation: Ishwar Singh et al. Ijppr.Human, 2022; Vol. 24 (2): 47-67.
67
J Pharm Res Technol. 2021;11(1):9–18.
55. Lagreca E, Onesto V, Di Natale C, La Manna S, Netti PA, Vecchione R. Recent advances in the
formulation of PLGA microparticles for controlled drug delivery. Prog Biomater. 2020;9(4):153–74.
56. Dubey M, Kesharwani P, Tiwari A, Chandel R, Raja K, Sivakumar T. Formulation and evaluation of
floating microsphere containing anti diabetic drug. Int J Pharm Chem Sci. 2012;1(3):1387–96.
57. Kosaraju SL, Lynette D, Lawrence A. Preparation and characterisation of chitosan microspheres for
antioxidant delivery. Food Chem Formul Sci. 2006;64(2):163–7.
58. Shantha KL, Harding DRK. Synthesis and characterisation of chemically modified chitosan microspheres.
Carbohydr Polym. 2002;48(3):247–53.
59. D Emanuele A, * RD. Preparation , characterisation , and drug release from thermoresponsive
microspheres. Int J Pharm. 1995;118(2):237–42.
60. Choudhury PK. Cellulose acetate microspheres as floating depot systems to increase gastric retention of
antidiabetic drug : formulation , characterization and In vitro – In vivo evaluation. Drug Dev Ind Pharm.
2008;34:349–54.
61. Maddiboyina B, Asthana A, Asthana GS, Singh S, Ramya M. Formulation and characterization of
polycarbophil coated mucoadhesive microspheres of repaglinide. J Pharm Sci Res. 2015;7(11):972–7.
62. Corbo MR, Bevilacqua A, Sinigaglia M. Original article Shelf life of alginate beads containing lactobacilli
and bifidobacteria : characterisation of microspheres containing Lactobacillus delbrueckii subsp . bulgaricus. Int
J Food Sci Technol. 2011;46:2212–7.
63. Dastidar DG, Saha S, Chowdhury M. Porous microspheres: synthesis, characterisation and applications in
pharmaceutical & medical fields. Int J Pharm. 2018;1(1):1–60.
64. Govender S, Pillay V, Chetty DJ, Essack SY, Dangor CM, Govender T. Optimisation and characterisation
of bioadhesive controlled release tetracycline microspheres. Int J ofPharmaceutics. 2005;306(1–2):24–40.
65. Jamini M, Rawat S. A review on microsphere. Res J Pharm Biol Chem Sci. 2013;4(1):1223–33.
66. Hu L, Zhang H, Song W. An overview of preparation and evaluation sustained-release injectable
microspheres. J Microencapsul. 2013;30(4):369–82.
67. Sharma M. In-vitro and in-vivo evaluation of repaglinide loaded floating microspheres prepared from
different viscosity grades of HPMC polymer. Saudi Pharm J. 2015;23(6):675–82.
68. Inamdar MN, Suresh S. Pharmacokinetic and pharmacodynamic evaluation of floating microspheres of
metformin hydrochloride. Drug Dev Ind Pharm. 2013;39(1):117–27.
69. Grace Rathnam* PB and AS. Nasal drug delivery of anti-diabetic drug repaglinide using degradable starch
microspheres. Int J Pharm Sci Res. 2011;2(4):940–7.
70. Caine M, Carugo D, Zhang X, Hill M, Dreher MR, Lewis AL. Review of the development of methods for
characterization of microspheres for use in embolotherapy : Translating bench to cathlab. Adv Healthc Mater.
2017;6(9):1–121.
71. Udmale A, J RR. A concise review on microspheres for targeted drug delivery. Int J Pharm Drug Anal.
2019;7(11):84–7.
