Quality by Design based formulation and evaluation of acyclovir microsponges

Abstract

Objective: The proposed study is focussed at developing acyclovir microsponges for oral drug delivery systems.  QbD was applied for better understanding of the process and to generate design space, using quality target product profile, critical quality attributes, and risk assessment. The aim of the experiment is to prepare a safe, efficacious, stable and patient compliant microsponge dosage form of Acyclovir. Materials and methods: Pre-formulation studies were carried out which helped in developing a suitable dosage form. UV, FTIR, DSC, and SEM studies were done for pre-formulation and post-formulation evaluations. QbD was applied to generate design space, using QTPP, CQA, and risk assessment. Microsponges of acyclovir were developed by 2³ factorial designs. Three variables Drug: Polymer ratio (X₁), Concentration of surfactant (X₂) and Stirring speed (RPM) (X₃) at two levels low and high were selected and response surface plots were generated. The microsponges were prepared by Quassi-emulsion solvent diffusion method. Various characterizations that were carried out include entrapment efficiency, percentage yield, particle size determination, in-vitro drug release studies and kinetic modelling of drug release. Statistical analyses of batches and surface response studies were done to understand the effect of various independent variables on the dependent variables. Results and Discussions: The λ_max was confirmed at 251 nm by UV spectroscopy. The melting point was determined experimentally to be 246⁰C which confirms the drug to be Acyclovir. FTIR and DSC studies confirmed that the drug is Acyclovir. Eight trials were taken as per the by 2³ factorial designs.  Conclusion: The study indicates that microsponges of Acyclovir by QbD approach were successfully developed.

Keywords: Microsponge, Acyclovir, DoE, QbD