Preparation and Evaluation of Controlled Release Acyclovir Microspheres Using Factorial Design

Abstract

Acyclovir, a synthetic purine nucleoside, is the most widely used antiviral agent. The short plasma half-life of oral acyclovir (3h) and low oral bioavailability (10-30%) with slow, variable and incomplete absorption through GIT requires high frequency dosing which may results in damaging side effects. Thus, the aim of present work is development of competent and efficient sustained release microspheres, to reduce the frequency of administration, to achieve patient compliance. Chitosan microspheres of acyclovir were prepared by ionotropic gelation where a 32 full factorial design was employed to study the effect of independent variables viz. chitosan concentration(X1), tripolyphosphate concentration(X1), and glutaraldehyde concentration(X1) on entrapment efficiency, drug loading and t50. Smooth, spherical microspheres with 16 to 95μ median particle size were obtained. The regression equations obtained were as follows, EE=32.332 + 8.033X1 - 0.495X2 + 1.343X3 - 0.491X1X2 - 0.730X1X3 - 0.448X2X3 + 0.355X1X2X3, DL=5.597 - 1.002X1 - 0.062X2 - 0.373X3 - 0.512X1X2 - 0.241X1X3 + 0.125X2X3 + 0.005X1X2X3, T50=148.51 + 48.49X1 + 27.72X2 + 41.30X3 + 15.11X1X2 + 16.32X1X3 + 10.16X2X3 + 6.63X1X2X3. ANOVA for results revealed that for obtaining controlled drug release with better microspheres properties relatively high levels of chitosan, tripolyphosphate and glutaraldehyde could be used.