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

• Published in: Journal of drug delivery science and technology 2020-12, Vol.60, p.102006, Article 102006
• Main Authors: Wani, Taha Umair, Mir, Khalid Bashir, Fazli, Abdul Aala, Raza, Syed Naiem, Khan, Nisar Ahmad
• Format: Article
• Language: English
• Subjects: Bioavailability; Extended drug release; Floating capsules; Gastroretentive; Pharmacokinetics
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2020.102006

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. [Display omitted] Capsules were placed in 900 ml of 0.1 N HCl maintained at 37 ± 0.5 °C and constantly stirred at 100 rpm using USP II dissolution apparatus. 5 ml samples were withdrawn from the medium after every hour. The medium was replenished with same volume (5 ml) of blank medium (0.1 N HCl) from the stock each time a sample was withdrawn in order to maintain the sink conditions. The samples were filtered through Whatman filter paper and suitable dilutions of the samples were prepared and analyzed for the absorbance using UV spectrophotometer (Cary 60 Agilent Technologies) at λmax 234 nm. Lactose as release rate modifier was used in different ratios to increase the amount of drug released from the formulations. None of the capsules did break open or burst during buoyancy or dissolution studies.