Design and development of novel lipid based gastroretentive delivery system: response surface analysis, in-vivo imaging and pharmacokinetic study

摘要

Famotidine HCl has low bioavailability (40–45%) due to its narrow absorption window and low solubility in intestinal pH. Lipids were utilized in the formulation of novel gastroretentive dosage forms to increase the availability of famotidine HCl at its absorption site. Novel non-swellable gastroretentive lipid disks (D) and swellable compression coated tablets with a lipid core (T) were prepared. Formulae were characterized by friability testing, in-vitro buoyancy, in-vitro drug release and scanning electron microscopy (SEM). Factorial designs of 22?×?31 and 32 were planned for the optimization of disks and tablets, respectively, using Design-Expert? software. X-ray imaging was used for the in-vivo visualization of the selected formula in human gastrointestinal tract (GIT). Moreover, a bioavailability study was performed in healthy human volunteers using the optimized disk formula (D10). Results showed that formulae D10 (containing stearyl alcohol and polyethylene glycol in a ratio of 9:1 w/w) and T7 (containing polyethylene oxide only) had highest desirability values (0.684 and 0.842, respectively). Lipids achieved instantaneous floating and sustained the release of famotidine HCl over a prolonged period of time with significant bioavailability enhancement.