Gastroretentive Drug Delivery System of Ranitidine Hydrochloride Based on Osmotic Technology: Development and Evaluation

摘要

Gastroretentive drug delivery systems (GRDDS) of Ranitidine hydrochloride (RHC) has been designed based on the osmotic technology, with the floating and swelling features in order to prolong the gastric retention time. The developed system consisted of osmotic core (containing drug, osmotic agent and hydrophilic polymers), coated with semipermeable membrane (SPM) which is then further coated with compression coating of gelling agent (HPMC K4M) containing gas generating agent (citric acid). All the developed formulations were evaluated for floating lag time, duration of floating, drug content and in-vitro drug release profile. Formulation variables like levels of hydrophilic polymer (0-18.26%w/w), type of plasticizer (PEG-400, Dibutyl phthalate), coat thickness of SPM (60-100μm), were found to affect the drug release from the developed formulations. Drug release was directly proportional to hydrophilic nature of plasticizer but inversely proportional to the levels of hydrophilic polymer and coat thickness of SPM. Drug release from developed formulations was independent of level of gas generating agent in compression coat, pH and agitation intensities of release media but dependent on osmotic pressure of the release media. All the developed formulation showed floating lag time of less than 2 min (desired) and were floated for more than 12 hr. Floating lag time was inversely related to level of citric acid in compression coat and directly related to the density of the developed formulations. The manufacturing procedure was found to be reproducible and formulations were stable after 3 months accelerated stability study. Prediction of steady state levels showed the plasma concentrations of RHC to be within desired range.