Determination of Target In-Vitro Drug Release Profile for Extended Release Formulation of Acyclovir through Pharmacokinetic Simulations

R.      Sankar; Subheet Kumar      Jain

doi:10.2174/2211352511311020014

Abstract

Acyclovir, a widely used anti-viral drug, is the treatment of choice for initial episodes and management of recurrent episodes of genital herpes. Oral immediate release (IR) formulations of acyclovir have limitations of poor and variable bioavailability (15-30%), and dosing frequency up to five times a day. Such limitations lead to poor patient compliance and development of drug resistance. An oral extended release (ER) formulation of acyclovir can overcome these limitations. In the present study, a simple simulation technique for determination of the dose and in-vitro drug release profile required for an ER formulation of acyclovir to achieve steady state maximum and minimum plasma concentrations ( C^ss_max and C^ss_min ) similar to or better than those of an IR formulation, has been reported. First order drug release and absorption models were used. The dose and in-vitro drug release rate required for the ER formulation were found to be 725 mg and 0.259 h-1, respectively. C^ss_max and C^ss_min values of the ER formulation were 90% and 218%, respectively, compared to those of the IR formulation. The fluctuation index of the ER formulation ( FI_ER ) was 69% of that of the IR formulation ( FI_IR ), indicating that the ER formulation can maintain more constant plasma concentrations than the IR formulation. Results of the simulation study indicated the feasibility of an ER formulation of acyclovir for twice daily administration. If the target in-vitro drug release and dose required for an ER formulation are known prior to initiation of formulation development, the number of experiments, cost and development time can be significantly reduced.

Keywords: Acyclovir, conventional delivery limitations, extended release, oral delivery, simulation model, target in-vitro drug release.