HPMC/Carbopol based extended release gastroretentive dosage form of losartan potassium: Formulation and in vivo pharmacokinetic evaluation in rabbits

Abstract

Novel HPMC/Carbopol based floating gastroretentive (GR) capsules were developed that provided extended release of losartan potassium (LP) in the upper region of gastrointestinal (GI) tract. The in vitro floating properties and drug release of capsules were evaluated in simulated gastric conditions (dissolution medium: 0.1 N HCl; 37 ± 0.5 °C; 100 rpm). In vivo buoyancy studies were performed in rabbits using X-ray radiographic technique. The capsules floated for >12 h in the dissolution medium and provided extended drug release with greater than 90% of the drug released over a period of 12 h. The X-ray images provided an evidence of gastric residence of >8 h. Pharmacokinetic evaluation was performed according to randomized crossover design using rabbits as animal models. The quantification of LP and its active metabolite, E3174 in plasma was performed using a validated HPLC method. Plasma concentration-time curves of LP and E3174 were plotted and pharmacokinetic (PK) parameters including MRT, t1/2, AUC, Cmax, Tmax and ke for both LP and E3174 were obtained. The results were compared with that of market formulation, Cozaar®. Except for the AUC of LP, the novel HPMC/Carbopol capsules had a significant effect on above mentioned PK parameters of LP as well as E3174. The relative bioavailabilities of the LP and E3174 were 126% and 140% respectively.