Formulation optimization of gastroretentive drug delivery system for allopurinol using experimental design.

Objectives: The objective of the study was to develop gastroretentive dosage form (GRDF) for allopurinol (ALP) using combined approaches of mucoadhesion and floating systems. GRDF was systematically optimized using 3(2)-full factorial design.

Methods: Concentrations of sodium carboxymethyl cellulose (X1) and concentration of polyoxyethylene oxide WSR 303 (X2) were selected as independent variables, whereas gastroretentive parameters like total floating time (TFT) (Y1), mucoadhesive force (MF) (Y2), time required for 10% drug release (Y3) and time required for 80% drug release (Y4) were selected as dependent variables in development of robust GRDF of ALP. GRDF was evaluated for gastroretentive parameters such as floating lag time (FLT) and TFT, MF using texture analyzer and ex vivo residence time using modified disintegration test apparatus. Roentgenography study of optimized formulation was conducted to evaluate in vivo gastro retentive behavior using albino rabbits.

Results: Developed tablets showed immediate in situ gas generation and exhibited FLT of 1.68 s after placing into simulated gastric fluid, which lead to buoyancy as well as controlled drug release for 24 h with zero-order drug release kinetics. The optimized formulation was selected based on in vitro drug release characteristics. In vivo retention of optimized formulation was corroborated using roentgenography studies.

Conclusion: The study concluded that the combination of mucoadhesive and floating approaches for GRDF aids to achieve desired gastroretentive performance and drug release properties for ALP. The formulation scientists may adopt these formulation strategies for drugs suitable for the development of GRDF.