A REVIEW ON MICROBEADS -PHARMACEUTICAL CARRIER DRUG DELIVERY SYSTEM

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A REVIEW ON MICROBEADS – PHARMACEUTICAL CARRIER
DRUG DELIVERY SYSTEM
Krishnaveni Manubolu1* and Yejerla Ratna Kumari2
1,2Faculty of Pharmaceutical Sciences, Narayana Pharmacy College, Nellore 524002.
ABSTRACT
This review discussed the usage of microbeads as a medication
delivery mechanism and natural polymers. Any drug delivery system's
purpose is to deliver a therapeutic amount of medicine to the
appropriate place in the body while also achieving and maintaining the
correct drug concentration. This could be accomplished using a
multiparticulate dosage form, such as beads, which are divided into
numerous separate pieces, known as subunits, each of which possesses
some desired features. The advantages of micro particle drug delivery
systems over single unit dose form are well documented. One of the
solutions that does not entail the use of harsh chemicals or elevated
temperatures is the production of microbeads medication delivery
systems. Conventional procedures include the use of ionotropic gelation, emulsion gelation,
polyelectrolyte complexation, and other methods. Because of the ease of preparation, the
majority of work has been done on the preparation of microbeads using the ionotropic
gelation process rather than alternative approaches. The ionotropic gelation approach relies
on the capacity of polyelectrolytes to crosslink with counter ions to generate a hydrogel
sustained release formulation.
KEYWORDS: Microbeads, controlled drug delivery, oral, natural polymer.
INTRODUCTION
Oral ingestion is the oldest and commonest mode of drug administration. It is
increasingly being used for the delivery of therapeutic agents due to its low cost, safety, ease
of administration and high levels of patient compliance. More than 50% of the drug delivery
systems available in market are oral drug delivery systems.[1] Sustained release-drug delivery
systems (SRDDS) provide drug release at a drug concentration which is maintained in the
World Journal of Pharmaceutical Research
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Volume 12, Issue 19, 70-79. Review Article ISSN 2277– 7105
*Corresponding Author
Krishnaveni Manubolu
Faculty of Pharmaceutical
Sciences, Narayana
Pharmacy College, Nellore
524002.
Article Received on
08 Sept. 2023,
Revised on 29 Sept. 2023,
Accepted on 20 Oct. 2023
DOI: 10. 20959/wjpr202319-29883

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therapeutic window for a prolonged period of time (sustained release), thereby ensuring
sustained therapeutic action. This allows the enhancement of duration of action of all short
half-life drugs, elimination of side effects, reducing frequency of dosing and wastage of
drugs, optimized therapy and better patient compliances.
Fig-1: Sustained release Drug Profile.
Type-2 Diabetes Mellitus is a disease of progressive beta-cell dysfunction in the presence of
insulin resistance, leading to loss of glycemic control. The pathological loss of beta cell may
be the result of a number of factors including:
1. β-cell secretory defects.
2. Glucotoxicity due to hyperglycemia.
3. Lipotoxicity due to dyslipidemia.
4. Possible abnormalities in secretion or response to incretin hormones.
 It usually develops in adults over the age of 45 years but is increasingly occurring in
younger age groups including children, adolescents and young adults.
 Is more likely in people with a family history of type 2 diabetes or from particular ethnic
backgrounds.
 For some, the first sign may be a complication of diabetes such as a heart attack, vision
problems or a foot ulcer
 Is managed with a combination of regular physical activity, healthy eating and weight
reduction.
 As type 2 diabetes is often progressive, most people will need oral medications and/or
insulin injections in addition to lifestyle changes over time.

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SUSTAINED RELEASE DRUG DELIVERY SYSTEM
Oral controlled drug delivery systems represent the most popular form of sustained drug
delivery systems for the obvious advantages of oral route of drug administration. Such
systems release the drug with constant or variable release rates. The oral controlled release
systems shows a typical pattern of drug release in which the drug concentration is maintained
in the therapeutic window for a prolonged period of time (sustained release), thereby ensuring
sustained therapeutic action. In recent years, scientific and technological advancements have
been made in the research and development of rate controlled oral drug delivery systems.
These formulations are designed to deliver the drugs at a pre determined rate, thus
maintaining their therapeutically effective concentration in systemic circulation for prolonged
periods of time.[3]
Microparticles are characteristically free flowing powders consisting of particles of size
rangigng from several tenths of a micron to 5 thousands microns. They consists proteins or
synthetic polymers which are biodegradable in nature. A well designed controlled drug
delivery system can overcome some of the problems of conventional therapy and enhance the
therapeutic efficacy of a given drug. Each particle is basically a mixture of drug, dispersed in
a polymer form with release occurs by first order process. Drug release is controlled by
dissolution/degradation of matrix. Microparticles are the drug loaded particles in micron size
where as microspheres are the drug loaded microparticles with a spherical shape which offer
a ball bearing effect.
Recent advances in polymer science and drug carrier technologies have promulgated the
development of novel drug carriers such as bioadhesive microspheres that have boosted the
use of "bioadhesion" in drug delivery.[4]
MECHANISM OF SUSTAINED RELEASE MICROBEADS
There are three main mechanisms involved in the release of drug from microspheres. It is
based upon the type of microspheres formulated whether matrix type or reservoir type. The
drug gets either diffused from the membrane or gets enzymatic lysis or hydrolysis when
exposed to thesurrounding gastric fluids.

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Fig.No:2- Mechanism of release of Microbeads.
ADVANTAGES OF SUSTAINED RELEASE MICROBEADS
 Control of drug therapy is achieved.
 Rate and extent of drug absorption can be modified.
 Frequency of drug administration is reduced.
 Patient compliance can be improved.
 Drug administration can be made convenient.
 Maximizing the availability of drug with minimum dose.
 The safety margin of high potency drugs can be increased.
DISADVANTAGES OF SUSTAINED RLEASE MICROBEADS
 Highly molecular weight compounds have a limited and restricted loading and their
release may be difficult.
 Formation of complexes with the blood components.
 There is high cost of production.
 There is reduced ability to adjust the dose.
 It is a highly sophisticated technology and requires skills to manufacture.
 It is difficult to maintain the stability of dosage form.
DRUG CANDIDATES FOR SUSTAINED RELEASE DOSAGE FORM
1. Drugs which are uniformly absorbed in GIT like Metformin, Vilgagliptin
2. Drugs which can be formulated even in smaller doses.

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3. The drugs having good margin of safety i.e. their therapeutic index should be in relative
range.
4. The drugs which do not show any cumulative action, any undesired side effect as in case
of dose dumping it might produce toxicity.
1.1.5 DRUG NON-CANDIDATES FOR SUSTAINED RELEASE DOSAGE FORM
1. The drugs which are absorbed and excreted rapidly like Pencillin-G and Furosemide.
2. The drugs with long biological half life (>12hrs) like Diazpam and Phenytoin.
3. The drugs which require to be administered in large doses (>1gm) like Sulfonamides.
4. The drugs having extensive binding of plasma proteins will have long elimination half
life and such drugs generally do not require to be formulated to SRDF.[5]
TECHNIQUES OF MANUFACTURE OF SUSTAINED RELEASE MICROBEADS
There are Several Techniques for the preparation of Microparticles These are as follows.[7]
 Single emulsion technique
 Double emulsion technique
 Polymerization technique
 Normal polymerization technique
 Interfacial polymerization technique
 Phase separation coacervation technique
 Spray drying & spray congealing technique
 Solvent extraction technique
 Solvent evaporation technique
 Solvent diffusion technique
 Ionotropic gelation technique.[7]
TYPES OF MICROPARTICLES
1. Bio-adhesive microparticles
Adhesion can be defined as sticking of drug to the membrane by using the sticking property
of the water soluble polymers. Adhesion of drug delivery device to the mucosal membrane
such as buccal, ocular, rectal, nasal etc can be termed as bio adhesion. These kinds of
microspheres exhibit a prolonged residence time at the site of application and causes intimate
contact with the absorption site and produces better therapeutic action.

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2. Magnetic microparticles
This kind of delivery system is very much important which localises the drug to the disease
site. In this larger amount of freely circulating drug can be replaced by smaller amount of
magnetically targeted drug. Magnetic carriers receive magnetic responses to a magnetic field
from incorporated materials that are used for magnetic microspheres are chitosan, dextran etc.
3. Therapeutic magnetic microparticles
Are used to deliver chemotherapeutic agent to liver tumour. Drugs like proteins and peptides
can also be targeted through this system.
4. Diagnostic microparticles
It can be used for imaging liver metastases and also can be used to distinguish bowel loops
from other abdominal structures by forming nano size particles supra magnetic iron oxides.
5. Floating microparticles
In floating types the bulk density is less than the gastric fluid and so remains buoyant in
stomach without affecting gastric emptying rate. The drug is released slowly at the desired
rate, if the system is floating on gasteric contentand increases gastric residence and increases
fluctuation in plasma concentration. Moreover it also reduces chances ofstriking and dose
dumping. One another way it produces prolonged therapeutic effect and therefore reduces
dosing frequencies. Drug (ketoprofen) given through this form.
6. Radioactive microparticles
Radio emobilisation therapy microspheres sized 10-30 nm are of larger than capillaries and
gets tapped in first capillary bed when they come across. They are injected to the arteries that
lead to tumour of interest. So all these conditions radioactive microspheres deliver high
radiation dose to the targeted areas without damaging thenormal surrounding tissues. It
differs from drug delivery system, as radio activity is not released from microspheres but acts
from within a radioisotope typical distance and the different kinds of radioactive microsphers
are α emitters, β emitters, γ emitters.
7. Polymeric microparticles
The diffenttypes of polymeric microspheres can be classified as followsand they are
biodegradable polymeric microspheres and Synthetic polymeric microspheres.

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8. Biodegradable polymeric micropaticles
The natural polymers such as starch are used with the concept that they are biodegradable,
biocompatible, and also bio adhesive in nature. Biodegradable polymers prolongs the
residence time when contact with mucous membrane due toit’s high degree of swelling
property with aqueous medium, results gel formation. The rate and extent of drug release is
controlled by concentration of polymer and the release pattern in a sustained manner. The
main drawback is, in clinical use drug loading efficiency of biodegradable microspheres is
complex and is difficult to control the drug release. However they provide wide range of
application in microsphere based treatment.
9. Synthetic polymeric microparticles
The interest of synthetic polymeric microspheres are widely used in clinical application,
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 kind of
microspheres, are tend to migrate away from injection site and lead to potential risk,
embolismand further organ damage. Differentkinds of polymers used for microsphere.[8]
POLYMERS USED IN FORMULATION OF MICROBEADS
In the formulation of FDDS, several polymers are used. They are classified into two types:
1. Synthetic Polymers
2. Natural Polymers
1. Synthetic Polymers
Fig. No. 3: Types of synthetic Polymers.
Non-biodegradable polymers:– Polymethyl Methacrylate, Glycidyl Methacrylate,
Acrylates.
Biodegradable polymers:– Lactides and Glycolides, Copolymers, Polyalkyl Cyano Poly
Anhydrides.
SYNTHETIC POLYMERS
Non-biodegradable
polymers
Biodegradable polymers

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2. Natural polymers
In recent years, polymers those are derived from plant origin have evoked tremendous
interest because of their diverse pharmaceutical applications. These natural gums and
Mucilages are preferred over the synthetic ones because they are biocompatible, cheap, and
easily available than the synthetic ones.
Table 1: Some Natural Gums Used in Formulation of controlled drug delivery
dosageforms.
Common Name
Botanical Name
Family
Reference
Okra Gum
Hibiscus esculentus
Malvaceae
[9]
Hibiscus Mucilage
Hibiscus rosasinensis. Linn
Malvaceae
[10,11,12]
Tamarind Seed
Polysaccharide
Tamarindus indica
Leguminoseae
[13]
Fenugreek mucilage
Trigonella foenum graecum
Leguminoseae
[14,15]
A. Okra Mucilage
The okra gum is obtained from the fresh fruits of the plant Abelmoschus esculentus (family
:malvaceae). The okra polysaccharide contains the major polysaccharide component
differing widely in the molar ratios of galactose, galacturonic acid, and rhamnose and with
some fractions of glucose, mannose, arabinose, and xylose. Mucilage from the pods of
Abelmoschus esculentus is evaluated for its safety and suitability as suspending agent.[9]
B. Hibiscus rosasinensis
Mucilage is obtained from fresh leaves of Hibiscus rosa-sinensis (family: malvaceae).
Mucilage of Hibiscus rosa-sinensis contains L-rhamnose, D-galactose, D-galacturonic acid,
and D-glucuronic acid. The use of its mucilage for the development of sustained release
tablet has been reported.[10]
C. Tamarind Seed Polysaccharide
Tamarind xyloglucan is obtained from the endosperm of the seed of the tamarind tree,
Tamarindus indica (family: fabaceae). Tamarind gum is a polysaccharide composed of
glucosyl: xylosyl: galactosyl in the ratio of 3: 2: 1. It was seen that the matrix tablets prepared
by using tamarind gum were able to carry most of the drug to the colon and restrict the
release in upper GIT.[13]

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D. Fenugreek Mucilage
This mucilage is obtained from seeds of Trigonella foenumgraceum (family: Leguminosae).
Its seeds contain a high percentage of mucilage and do not dissolve in water but form viscous
tacky mass and swell up when exposed to fluids.[14]
FORMULATION LIST
Table 2: List of Drugs Formulated with controlled drug delivery.
S. No
Dosage Form
Drugs
1.
Reservoir System tablet
Morphine sulfate
2.
Matrix system tablet
Isosorbite mononitrate, Metformin HCl,
Clarithromycin
3.
Diffusion controlled release
Bupropion
4.
Push pull osmotic system
Doxazosin, Verapamil, Glipizide
5.
Ion-Exchange System
Hydrocodon, Dextromethorphan
6.
PH dependent system
Aceclofenac, Diclofenac sodium
7.
Altered density formulation
Levodopa and benserazide.[5]
MARKETD PRODUCTS LIST
Table 3: List of Marketed Products of SRDDS.
S. No
Drug
Brand Name
1.
Metformin HCL
Glucomet®SR
2.
Isosorbite mononitrate
Imdura®
3.
Verapamil
Covera HS
4.
Glipizide
Glucotrol XL
5.
Aceclofenac
Hifenac SR
6.
Propranolol HCL
Inderal® LA5.
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