The objective of this study was to formulate and evaluate a gastroretentive floating drug delivery system (GFDDS) for Dolutegravir, a potent integrase strand transfer inhibitor used in HIV therapy. Due to Dolutegravir's narrow absorption window and enhanced solubility in acidic conditions, a floating system was designed to prolong gastric residence and improve oral bioavailability. Various polymeric formulations (F1– F21) were developed using hydroxypropyl methylcellulose (HPMC) and glyceryl behenate in different drug-topolymer ratios. The formulations were evaluated for pre-compression and post-compression characteristics including flow properties, hardness, friability, drug content, in vitro buoyancy, and dissolution profiles. The optimized formulation F7, demonstrated satisfactory physicochemical properties, floating lag time of less than one minute, and sustained buoyancy for over 12 hours. It showed a cumulative drug release of 94.32% over 12 hours, following Higuchi kinetics and non-Fickian diffusion, suggesting controlled release through a combination of diffusion and erosion. Comparative studies with marketed formulation (Tivicay) and pure drug indicated enhanced release kinetics and retention within the stomach. The compatibility between the drug and excipients was established using differential scanning calorimetry, while scanning electron microscopy revealed a consistent and homogeneous surface structure. The developed system showed significant promise as a gastroretentive platform for improving the therapeutic performance of Dolutegravir. The findings validate the potential of floating tablets as a strategy for antiretroviral drugs with limited absorption windows, thus enhancing patient compliance and therapeutic outcomes.
Shareef et al. (Tue,) studied this question.