Multiunit floating drug delivery system of acyclovir: Development, characterization and in vitro-in vivo evaluation of spray-dried hollow microspheres

摘要

Acyclovir, anti-herpes virus drug, was loaded in hollow microspheres to improve bioavailability and patient compliance by prolonging the residence time in the gastrointestinal tract. The hollow microspheres of acyclovir were prepared by spray-drying method using ethyl cellulose as a drug-controlled release polymer. We found that the selected process parameters of spray-drying method like inlet temperature, outlet temperature, spray flow rate and vacuum pressure can give rise to hollow microspheres with good yields of production, high drug content and buoyancy, narrow size distribution and good encapsulation efficiency. The size of the microspheres prepared from different ratios of acyclovir and ethyl cellulose was 1.1-2.7 μm. When the drug:polymer ratio was increased, the size and percent drug content increased. The hollow microspheres having higher polymer concentrations were less buoyant than those with lower polymer concentrations. The formulation HSF1 showed the highest buoyancy of 94.18 ± 4.4%. Dissolution profiles indicate that when drug:polymer ratio increased from 1:2 to 1:6, a decrease in release rate was observed. The highest correlation coefficient was obtained in first-order release model as compared to zero-order followed by Higuchi model. From the Higuchi plot it was found that drug release from the microspheres was diffusion type. The 'n' values from Korsmeyer-peppas model indicated that all three formulations follow Fickian diffusion controlled release. The AUC values for oral administration of selected formulation and conventional tablet (Zovirax) clearly indicated two- to three-fold improvement in the bioavailability of acyclovir from prepared formulation when compared to conventional commercial tablet.