Irjpas 3 (3) 24-28 PDF
Irjpas 3 (3) 24-28 PDF
Irjpas 3 (3) 24-28 PDF
Review Article
VARIABLES EFFECTING DRUG ENTRAPMENT EFFICIENCY OF MICROSPHERES: A
REVIEW
Kaur Dupinder*, Saini Seema
Rayat Institute Of Pharmacy, Department Of Pharmaceutics, Ropar. S.B.S.Nagar-144533(Punjab) India
. (Received: 20 May 2013; Accepted: 28 May, 2013; Published: 30 June, 2013)
Corresponding Author’s email: kaurdupinder69@gmail.com
Abstract: Microspheres are characteristically free flowing powders consisting of proteins or synthetic polymers which are
biodegradable in nature and ideally having a particle size less than 200 μm. A well designed microsphere can overcome such
problems by enhancing the loading efficiency of a particular drug and minimizing the wastage of drug. 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. For success of microspheres as drug delivery system its necessary to obtained desired particle size, maximum drug
entrapment, mucoadhesion, swelling index and drug release. This can be obtained by optimizing the formulation as well as
process variables but before designing the microspheres formulation deep understanding the effect of various variables on
characteristics of microspheres is necessary. The intent of the paper is to highlight the reported study on various formulation
variables those are might be useful to encountered several problems which is reason for low drug entrapment efficiency
Keywords: Novel drug delivery system, Controlled release, Microspheres, Drug entrapment.
drug in the solid form is then dispersed in the polymer from which the solvent evaporates instantaneously leading
solution under high speed homogenization. This dispersion the formation of the microspheres in a size range 1-100 μm.9
is then atomized in a stream of cold air. The atomization
leads to the formation of the small droplets or the fine mist 3. Solvent Evaporation
Fig-1: The processes are carried out in a liquid are prepared by single emulsion technique. The natural
manufacturing vehicle. The microcapsule coating is polymers are dissolved or dispersed in aqueous medium
dispersed in a volatile solvent which is immiscible with the followed by dispersion in the non aqueous medium e.g., oil.
liquid manufacturing vehicle phase. A core material to be In the second step of preparation, cross linking of the
microencapsulated is dissolved or dispersed in the coating dispersed globules carried out. The cross-linking agents can
polymer solution. With agitation the core material mixture is be achieved either by means of heat or by using cross-
dispersed in the liquid manufacturing vehicle phase to linking agents used include glutaraldehyde, formaldehyde,
obtain the appropriate size microsphere. The mixture is then diacid chloride, etc. cross linking by heat is affected by
heated if necessary to evaporate the solvent. The solvent adding the dispersion to previously heated oil. Heat
Evaporation technique to produce microspheres is denaturation is however, not suitable for the thermoliable
applicable to wide variety of core materials. 10 drugs while the chemical cross-linking suffers disadvantage
of excessive exposure of active ingredient to chemical cross-
4. Single emulsion technique linking suffers disadvantage of excessive exposure of active
The microspheres can be prepared by using any of ingredient to chemicals if added at the time of preparation
natural polymers, i.e. those of proteins and carbohydrates fig2.
It is carried out using different techniques as bulk, high polymer concentration results large size of
suspension, precipitation, emulsion and micellar microspheres which result in loss of drug from surface
polymerization processes. In bulk, a monomer or a mixture during washing of microspheres is very less as compare to
of monomers along with the initiator or catalyst is usually small microspheres. The encapsulation efficiency of the
heated to initiate polymerization. Polymer so obtained may microspheres improved as the polymer concentration
be moulded as microspheres. Drug loading may be done increase in oil phase and PVA concentration decreased in
during the process of polymerization. Suspension aqueous phase.
polymerization also referred as bead or pearl
polymerization. Here it is carried out by heating the 2. Drug: Polymer Ratio (DPR):
monomer or mixture of monomers as droplets dispersion in The drug entrapment efficiency within microspheres
a continuous aqueous phase. The droplets may also contain decreases when ratio of DPR increases. The encapsulation
an initiator and other additives. Emulsion polymerization efficiency is significantly increasing as the DPR decreased.
differs from suspension polymerization as due to the The encapsulation efficiency of microspheres significantly
presence initiator in the aqueous phase, which later on increase as the amount of polymer is increased at the same
diffuses to the surface of micelles. Bulk polymerization has amount of drug in the dispersed. 18
an advantage of formation of pure polymers.
3. Interaction between drug and polymer:
II. Interfacial polymerization Interaction between protein and polymer contributes to
It involves the reaction of various monomers at the increasing encapsulation efficiency.19 Generally, proteins are
interface between the two immiscible liquid phases to form capable of ionic interactions and are better encapsulated
a film of polymer that essentially envelops the dispersed within polymers that carry free carboxylic end groups than
phase.12 the end-capped polymers. On the other hand, if hydrophobic
interaction is a dominant force between the protein and the
7. Phase separation coacervation technique polymer, relatively hydrophobic end-capped polymers are
This process is based on the principle of decreasing the more advantageous in increasing encapsulation efficiency.20
solubility of the polymer in organic phase to affect the In certain cases, a co-encapsulated excipient can mediate the
formation of polymer rich phase called the coacervates. In interaction between protein and polymer.21 For example;
this method, the drug particles are dispersed in a solution of encapsulation efficiency increased when gamma
the polymer and an incompatible polymer is added to the hydroxypropyl cyclodextrin (g-HPCD) were co-
system which makes first polymer to phase separate and encapsulated with tetanus toxoid in PLGA microparticles. It
engulf the drug particles. Addition of non-solvent results in is supposed that the g-HPCD increased the interaction by
the solidification of polymer. Poly lactic acid (PLA) accommodating amino acid side groups of the toxoid into its
microspheres have been prepared by this method by using cavity and simultaneously interacting with PLGA through
butadiene as incompatible polymer. The process variables Van-der Waals and hydrogen bonding forces.
are very important since the rate of achieving the
coacervates determines the distribution of the polymer film, 4. Solubility of drug in continuous phase:
them particle size and agglomeration of the formed particles. If the drug is more soluble in continuous phase, more
The agglomeration must be avoided by stirring the drug loss in the continuous phase is occurs due to diffusion
suspension using a suitable speed stirrer since as the process of drug from dispersed phase to continuous phase. If the
of microspheres formation begins the formed polymerize solubility of the drug in the continuous phase is higher than
globules start to stick and form the agglomerates. Therefore in the dispersed phase, the drug will easily diffuse into the
the process variables are critical as they control the kinetic continuous phase during this stage which tends to decrease
of the formed particles since there is no defined state of the encapsulation efficiency. For example, the encapsulation
equilibrium attainment.13 efficiency of quinidine sulfate was 40 times higher in the
alkaline continuous phase (pH 12), in which quinidine
Factors influencing drug entrapment efficiency of sulfate is insoluble) than in the neutral continuous phase (pH
microspheres: 7), in which quinidine sulfate is very soluble. 22
1. Concentration of the polymer in dispersed phase:
Encapsulation efficiency increases with increasing 5. Effect of concentration of emulsifier:
polymer concentration For example, the encapsulation Thakkar et al investigated the effect of emulsifier on
efficiency increased from 53.1 to 70.9% when concentration the size, encapsulation efficiency and drug entrapment of the
of the polymer increased from 20.0 to 32.5% .14 High microspheres prepared using a natural polymer (bovine
viscosity and fast solidification of the dispersed phase serum albumin) BSA using emulsification chemical cross-
contributed to reduce porosity of the microparticles as linking method. Results from this investigation shows that
well.15 The contribution of a high polymer concentration to increase in concentration of Span-85 decrease the
the loading efficiency can be interpreted in three ways. First, encapsulation efficiency of microspheres in some extent.
when highly concentrated, the polymer precipitates faster on This is due to fact that increase in Span-85 concentration
the surface of the dispersed phase and prevents drug leads to stabilization of small droplets and results in smaller
diffusion across the phase boundary.16 Second, the high microspheres. Loss of drug from surface of small
concentration increases viscosity of the solution and delays microspheres is more as compared to larger microspheres
the drug diffusion within the polymer droplets.17 Third, the
during washing [23]. Drug loading decreased as the Even though it is generally assumed that fast polymer
concentration of DCM was increased.24 solidification results in high encapsulation efficiency. 28
Here, the encapsulation efficiency was not affected by the
6. Effect of method of preparation: solvent evaporation temperature. It may be due to the
The solvent evaporation method is popularly used for different processing temperatures influenced not only the
microsphere preparation because of its simplicity, rate of polymer solidification but also the diffusivity of the
reproducibility, and fast processing with minimum protein and its solubility in water. While the high
controllable process variables that can be easily temperature facilitated solidification of the dispersed phase,
implemented. But it is frequently used for water insoluble it enhanced diffusion of the protein into the continuous
drugs, as the entrapment efficiency of water-soluble drugs is phase, compromising the positive effect from the fast
low due to drug loss from the organic emulsified polymeric solidification.
phase before solidification of polymer in the microspheres.
10. Effect of cross linking agent concentration:.
7. Effect of Different Stirring Rates on Drug Content: Higher the conncenteration of cross linking agent then
The stirring rate of emulsion system is one of the higher will be the entrapment efficiency. The higher amount
frequently studied process parameters in microspheres of glutaraldehyde appears to favor the cross-linking
technology. The effect of this parameter on reaction, and hence spherical free-flowing microspheres
biopharmaceutical properties of microspheres containing were obtained with an increase in loading efficiency.29
drug and matrix polymer was often observed. The drug
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