International Journal of Trend in Scientific Research and Development (IJTSRD)

Volume 4 Issue 6, September-October 2020 Available Online: www.ijtsrd.com e-ISSN: 2456 – 6470

Review on Novel Drug Delivery System of Microsphere:

Type, Material, Method of Preparation and Evaluation
Suraj Rangnath Tandale, Mahesh Muralidhar Mole, Vitthal Ramdas Gawade
Rajarshri Shahu College of Pharmacy, Buldana, Maharashtra, India

ABSTRACT How to cite this paper: Suraj Rangnath

The Non ideal pharmaceutical, pharmacokinetic, and therapeutic properties Tandale | Mahesh Muralidhar Mole |
often combine to reduce the effectiveness of certain compounds. For the Vitthal Ramdas Gawade "Review on Novel
vectoring of such compounds to target areas, liposomes, nanoparticles, and Drug Delivery System of Microsphere:
microspheres have been suggested. Microsphere are spherical in shape so, Type, Material, Method of Preparation and
therapeutic efficacy of microspheres containing drug depends upon their Evaluation"
characteristics that can be altered in required terms by altering materials, , Published in
methods, polymers or techniques of microsphere. International Journal
of Trend in Scientific
Microspheres are characteristically free flowing powders having particle size
Research and
ranging from 1-1000 μm consisting of natural or synthetic polymers.
Development (ijtsrd),
Microspheres are used in drug delivery systems which are prepared to obtain
ISSN: 2456-6470, IJTSRD35725
prolonged or controlled drug delivery to improve bioavailability, stability and
Volume-4 | Issue-6,
action at the specific site to predetermined rate.
October 2020, pp.1545-1551, URL:
Microsphere can be manufactured by various type of material natural, and www.ijtsrd.com/papers/ijtsrd35725.pdf
synthetic in microsphere. Microspheres are various types like Bioadhesive
microspheres, Magnetic microspheres, Floating microspheres, radioactive Copyright © 2020 by author(s) and
microspheres, Polymeric microspheres, Biodegradable polymeric International Journal of Trend in Scientific
microspheres, Synthetic polymeric microspheres. microspheres and are Research and Development Journal. This
prepared by methods like Spray Drying, Solvent Evaporation, Single emulsion is an Open Access article distributed
technique, Double emulsion technique, Phase separation coacervation under the terms of
technique, Spray drying and spray congealing, Solvent extraction, Quassi the Creative
emulsion solvent diffusion. Microspheres have wide range of applications and Commons Attribution
their evaluation parameter. License (CC BY 4.0)
(http://creativecommons.org/licenses/by/4.0)

INTRODUCTION
A well designed controlled drug delivery system can throughout the microspheres matrix. Solid biodegradable
overcome some of the problems of conventional therapy and microspheres incorporating a drug dispersed or dissolved
enhance the therapeutic efficacy of a given drug. through particle matrix have the potential for the controlled
release of drug. They are made up of polymeric, waxy, or
To obtain maximum therapeutic efficacy, it becomes other protective materials, that is, biodegradable synthetic
necessary to deliver the agent to the target tissue in the polymers and modified natural products.[2]
optimal amount in the right period of time there by causing
little toxicity and minimal side effects [1] ADVANTAGES OF MICROSPHERES [3,4,5,6]
1. They provide protection before after administration for
There are various approaches in delivering a therapeutic unstable drug.
substance to the target site in a sustained controlled release 2. They reduced concentration of drug at site other than
fashion. One such approach is using microspheres as carriers the tissue or the target organ.
for drugs. 3. Decrease dose and toxicity.
4. Particle size reduction for enhancing solubility of poorly
MICROSPHERE Microspheres are solid spherical particles soluble drugs.
ranging in size from 1-1000µm. They are spherical free 5. Microspheres provide constant and prolonged
flowing particles consisting of proteins or synthetic therapeutic effect.
polymers. The microspheres are free flowing powders 6. Reduces the dosing frequency and thereby improve the
consisting of proteins or synthetic polymers, which are patient compliance.
biodegradable in nature. 7. They could be injected into the body due to the spherical
shape and smaller size.
There are two types of microspheres; 8. Better drug utilization will improve the bioavailability
Microcapsules. and reduce side effect.
Micromatrices. 9. Taste and odour masking.
10. Conversion of oils and other liquids to solids for easy of
Microcapsules are those in which entrapped substance is handling.
distinctly surrounded by distinct capsule wall and 11. Protection of drugs against the environment (moisture,
micromatrices in which entrapped substance is dispersing light etc.).

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 International Journal of Trend in Scientific Research and Development (IJTSRD) @ www.ijtsrd.com eISSN: 2456-6470
12. Improvement of flow of powders. magnetically targeted drug. Magnetic carriers receive
13. Aid or helps in the dispersion of water-insoluble magnetic responses to a magnetic field from incorporated
substances in aqueous media. materials that are used for magnetic microspheres are
chitosan, dextran etc. The different types are therapeutic
Disadvantage of microsphere [7] magnetic microspheres and diagnostic microspheres [8,9]
1. The costs of the materials and processing of the
controlled release preparation, are substantially higher 1. Therapeutic magnetic microspheres It is used to
than those of standard formulations. deliver chemotherapeutic agent to liver tumour. Drugs
2. The fate of polymer matrix and its effect on the like proteins and peptides can also be targeted through
environment. this system.
3. The fate of polymer additives such as plasticizers, 2. Diagnostic microspheres It can be used for imaging
stabilizers, antioxidants and fillers. liver metastases and also can be used to distinguish
4. Reproducibility is less. bowel loops from other abdominal structures by
5. Process conditions like change in temperature, pH, forming nano size particles supramagnetic iron oxides.
solvent addition, and evaporation/agitation may
influence the stability of core particles to be C. Floating microspheres:
encapsulated. In floating types the bulk density is less than the gastric fluid
6. The environmental impact of the degradation products and so remains buoyant in stomach without affecting gastric
of the polymer matrix produced in response to heat, emptying rate. The drug is released slowly at the desired
hydrolysis, oxidation, solar radiation or biological agents rate, if the system is floating on gastric content and increases
[7]. gastric residence and increases fluctuation in plasma
concentration. More over it also reduces chances of striking
Materials and dose dumping. One another way it produces prolonged
Microspheres used usually are polymers. They are classified therapeutic effect and therefore reduces dosing
into two types: frequencies.[10]
Synthetic Polymers
Natural polymers D. Radioactive microspheres
Radio immobilization therapy microspheres sized 10-30 nm
Synthetic polymers are divided into two types. is of larger than capillaries and gets tapped in first capillary
A. Non-biodegradable polymers bed when they come across. They are injected to the arteries
Poly methyl methacrylate (PMMA), Acrolein, Glycidyl that lead to tumour of interest. So all these conditions
methacrylate, Epoxy polymers radioactive microspheres deliver high radiation dose to the
targeted areas without damaging the normal surrounding
B. Biodegradable polymers tissues. It differs from drug delivery sys-tem, as radio
Lactides, Glycolides & their co polymers, Poly alkyl activity is not released from microspheres but acts from
cyanoacrylates, Poly anhydrides. within a radioisotope typical distance and the different kinds
of radioactive microspheres.
C. Natural polymers
Obtained from different sources like proteins, carbohydrates E. Polymeric microspheres
and chemically modified carbohydrates. The different types of polymeric microspheres can be
classified as follows and they are biodegradable polymeric
Proteins: microspheres and synthetic polymeric microspheres.
Albumin, Gelatin, Collagen
1. Biodegradable polymeric microspheres
Carbohydrates: Natural polymers such as starch are used with the concept
Agarose, Carrageenan, Chitosan, that they are biodegradable, biocompatible, and also
bioadhesive in nature. Biodegradable polymers prolongs the
Starch Chemically modified carbohydrates: residence time when contact with mucous membrane due to
Poly dextran, Poly starch its high degree of swelling property with aqueous medium,
results gel formation. The rate and extent of drug release is
TYPES OF MICROSPHERES controlled by concentration of polymer and the release
A. Bio adhesive microspheres: pattern in a sustained manner. The main drawback is in
Adhesion can be defined as sticking of drug to the membrane clinical use drug loading efficiency of biodegradable
by using the sticking property of the water soluble polymers. microspheres is complex and is difficult to control the drug
Adhesion of drug delivery device to the mucosal membrane release [11].
such as buccal, ocular, rectal, nasal etc can be termed as bio
adhesion. These kinds of microspheres exhibit a prolonged 2. Synthetic polymeric microspheres
residence time at the site of application and causes intimate The interest of synthetic polymeric microspheres are widely
contact with the absorption site and produces better used in clinical application, moreover that also used as
therapeutic action. bulking agent, fillers, embolic particles, drug delivery
vehicles etc and proved to be safe and biocompatible. But the
B. Magnetic Microspheres: main disadvantage of these kinds of microspheres, are tend
This kind of delivery system is very much important which to migrate away from injection site and lead to potential risk,
localizes the drug to the disease site. In this larger amount of embolism and further organ damage [12] . as radio activity is
freely circulating drug can be replaced by smaller amount of not released from microspheres but acts from within a

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radioisotope typical distance and the different kinds of emitters.[13]
radioactive microspheres’ are a emitters, ß emitters, g

Method of Preparation: [14,15,16]

Method of Preparation
Quassi
Single Double Phase separation Spray
Spray Solvent Solvent Emulsion
Emulsion Emulsion Coacervation Drying And spray
drying evaporation extraction Solvent
technique technique technique congealing
diffusion

1. Spray Drying
In Spray Drying technique, firstly the entire polymer are dissolved in a suitable volatile organic solvent such as
dichloromethane, acetone, etc. and then the drug in the solid form is dispersed in the polymer solution with high-speed
homogenization. This dispersion is then atomized in a stream of hot air. The atomization leads to the formation of the small
droplets or the fine mist from which the solvent evaporates instantaneously leading the formation of the microspheres in a size
range 1-100μm. Micro particles are separated from the hot air by means of the cyclone separator while the trace of solvent is
removed by vacuum drying. One of the major advantages of this process is feasibility of operation under aseptic conditions.

Fig.1 Spray drying technique

2. Solvent Evaporation:
This process are carried out in vehicles in this the two phases aqueous and organic phase that process called as emulsification
i.e. o/w type emulsion after this the solvent evaporate and remains raw nanospheres of microspheres.

Fig. 2 Solvent evaporation

3. Single emulsion technique:

In this technique aqueous solution of polymer are dispersed in organic phase oil/chloroform with continuous stirring this
process called as sonification. After this microsphere can be prepared by two ways, first heat denaturation and chemical cross
linking and centrifuge the product and washing or finally separation to produce microspheres.

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Fig.3 Single emulsion techniques

4. Double emulsion technique:

In this method aqueous solution of polymer and drug are dispersed in organic phase which produce first emulsion after
addition of aq. Solution of PVA and make multi emulsion in solution separation, washing and drying to produce microspheres.

Fig.4 Double emulsion technique

5. Phase separation coacervation technique:

In this technique aqueous/organic solution of drug dissolved in polymer solution that forms polymer rich globules or droplets
and Harding in aqueous/organic phase, separation, of microspheres washing and then drying to pure form of microspheres.

Fig. 5 Phase separation coacervation technique

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 International Journal of Trend in Scientific Research and Development (IJTSRD) @ www.ijtsrd.com eISSN: 2456-6470
6. Spray drying and spray congealing:
Polymer dissolved in suitable volatile organic solvent such as acetone, chloroform, etc. dissolved in polymer solution under
high speed homogenization atomized in stream of hot air and this lead to formation of small droplets and then solidifying and
form of minute particles.

Fig.6 Spray drying and spray congealing

7. Solvent extraction:
In the solvent extraction polymer and drug must be soluble in organic solvent which forms a solution that called aq. Phase and
extract this solution with water missible organic solvent to produce microsphere in aqueous media

Fig.7 Solvent extraction technique

8. Quassi emulsion solvent diffusion:

A novel quasi-emulsion solvent diffusion method to manufacture the controlled release microspheres of drugs with acrylic
polymers has been reported in the literature. Microsponges can be manufactured by a quasi emulsion solvent diffusion method
using an external phase containing distilled water and polyvinyl alcohol. The internal phase consists of drug, ethanol and
polymer. The concentration of polymer is in order to enhance plasticity. At first, the internal phase is manufactured at 60.C and
then added to the external phase at room temperature. After emulsification process, the mixture is continuously stirred for 2
hours. Then the mixture can be filtered to separate the microsponges. The product is then washed and dried by vacuum oven at
40o C.

Evaluation of microsphere:
1. Particle size and shape
2. The most widely used procedures to visualize micro particles are conventional light microscopy (LM) and scanning
electron microscopy (SEM).
3. Electron spectroscopy for chemical analysis:
4. The surface chemistry of the microspheres can be determined using the electron spectroscopy for chemical analysis
(ESCA)[15].
5. Density determination: The density of the microspheres can be measured by using a multi volume pycnometer [16].
6. Isoelectric point: The micro electrophoresis is used to measure the electrophoretic mobility of microspheres from which
the isoelectric point can be determined [17].
7. Angle of contact: The angle of contact is measured to determine the wetting property of a micro particulate carrier [18].

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8. In vitro methods: Release studies for different type of microspheres are carried out by using different suitable dissolution
media, mostly by rotating paddle apparatus (USP / BP) [19].
9. Drug entrapment efficiency: Drug entrapment efficiency can be calculated using following equation, % Entrapment =
Actual content/Theoretical content x 100.
10. Swelling index: The swelling index of the microsphere was calculated by using the formula, Swelling index= (mass of
swollen microspheres - mass of dry microspheres/mass of dried microspheres) [20].

Fig. 8 Application of Microsphere

Conclusion:
Microsphere can be manufactured by various type of [4] Nikam VK et el, Microspheres - A Novel Drug Delivery
material such as polymers, and microspheres. Microspheres System: An Overview, international journal of
are various types like Bioadhesive microspheres, Magnetic pharmaceutical and chemical sciences, 2012; 1(1)
microspheres, Floating microspheres, radioactive
[5] Kavita Kunchu, Raje Veera Ashwani et al. Albumin
microspheres, Polymeric microspheres, Biodegradable
Microspheres: A Unique system as drug delivery
polymeric microspheres, Synthetic polymeric microspheres
carriers for non steroidal anti-inflammatory drugs.
their method of preparation, evaluation and application of
2010; 5(2):12.
microscope.
[6] Divya thakur m. pharm, presentation on introduction,
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