Systematic development of a gastroretentive fixed dose combination of lamivudine and zidovudine for increased patient compliance

Abstract

The present study describes systematic development of a gastroretentive bilayer tablet formulation containing fixed dose combination of lamivudine and zidovudine exhibiting controlled drug release and floating-bioadhesive characteristics. Effervescent floating-bioadhesive bilayer tablets containing rational blend of polymers were formulated by non-aqueous granulation employing isopropyl alcohol. A face centred cubic design was employed for optimizing various critical material attributes of the bilayer tablets, which were evaluated for bioadhesive strength (BS), buoyancy time (Tb) and drug release characteristics as the critical quality attributes for each layer. The optimum composition for each layer was selected by “trading off” the magnitude of various quality attributes by maximization of BS, Tb and drug release characteristics, and demarcated in the design space. Gamma scintigraphic studies in healthy volunteers indicated gastroretentive behaviour of the optimized formulation upto 6 h, while the marketed immediate release formulation taken as control showed maximum gastroretentivity only upto 1 h. In a nutshell, these studies corroborated development of an optimal and stable once-a-day controlled release gastroretentive system of lamivudine and zidovudine.