MICROENCAPSULATION OF ALLOPURINOL USING A FULLY IMPROVED NON-SOLVENT ADDITION TECHNIQUE AND A NOVEL BINARY BLEND BASED ON POLYVINYL CHLORIDE: FACTORIAL DESIGN APPLICATION

El-Gibaly, Ibrahim

doi:10.21608/bfsa.1998.67984

MICROENCAPSULATION OF ALLOPURINOL USING A FULLY IMPROVED NON-SOLVENT ADDITION TECHNIQUE AND A NOVEL BINARY BLEND BASED ON POLYVINYL CHLORIDE: FACTORIAL DESIGN APPLICATION

Document Type : Original Article

Author

Ibrahim El-Gibaly

Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt

10.21608/bfsa.1998.67984

Abstract

A fully improved non-solvent addition coacervation-phase separation process which utilizes tetrahydrofurfuryl alcohol – cyclohexane : hexane (1:1 v/v ratio) as a solvent-non solvent pair, a novel binary blend comprising of polyvinyl chloride in combination with poloxamer 188 [a triblock copolymer of poly (ethylene oxid) – poly (propylene oxide) – poly (ethylene oxide)] as the wall material and ethylene-vinylacetate copolymer or polyisobutylene as coacervation-inducing agents has been developed for encapsulating allopurinol. The role of the coaddition of dioctylphthalate as a plasticizer and poloxamer 188 as a complementary coating polymer to the polymer solution phase on the properties of the microcapsules was investigated. The results indicated that plasticized / blended microcapsules resulted in a great shift to a narrow particle size distribution and a significant reduction in the drug loss percentage and the drug release rate in comparison with unplasticized / unblended microcapsules or plasticized polyvinyl chloride microcapsules.
In the preparation of the plasticized / blended microcapsule formulations, a 2³ full factorial design based on three independent variables viz.; polymers blend concentration, amount of allopurinol and the type of the coacervation-inducing agent was applied. The mean influences of these variables on the micromeritic parameters (geometric mean particle diameter, span value and drug content) and dissolution properties of the microcapsules were characterized quantitatively and represented by predictor polynomial equations. The kinetic model according to the Rosin-Rimmler-Sperling-Bennett-Weillbull (RRSBW) distribution was applied for the linearization and parametric representation of the dissolution curves. The surface morphology of the microcapsules was examined by using scanning electron microscopy. The results revealed that using a lower polymers blend concentration level, a higher drug loading and ethylene-vinylacetate copolymer as a coacervation-inducing agent resulted in the formation of fairly spherical microcapsules of high monodispersity and better surface characteristics and extended the drug release period (t: time at which 63.2 percent of the medicament dissolved = 6.052 h in simulated gastric fluid (S.G.F, pH 1.2) – 5.151 h in simulated intestinal fluid (S.I.F, pH 7.4). in contrast, polyisobutylene microcapsules prepared under the same experimental conditions were irregular, macroporous, and having the fastest release rate (t= 4.48 h (S.G.F, pH 1.2) – 2.051 h (S.I.F, pH 7.4)). Studies of the drug release thermodynamics by the Arrhenius equation demonstrated clearly that the release of allopurinol is an energy-linked process by a single release mechanism. The formulation of microcapsules prepared using ethylene-vinylacetate copolymer into tablets, prolonged greatly the drug release.