FLOATING DRUG DELIVERY SYSTEM AS AN APPROACH TO INCREASE THE GASTRIC RETENTION OF METHOTREXATE: FORMULATION AND EVALUATION

摘要

The objective of the present study is to develop and characterize floating microspheres of methotrexate, which after oral administration could prolong the gastric residence time and increase the bioavailability of the drug, in order to provide the sustained release to minimize the dose dependent side effects as well as to improve patient compliance. Another aim is to investigate drug release at slight higher pH, which is due to frequent administration of water to make dosage form floating. The porous microspheres containing (1) methotrexate – antineoplastic agent, (2) casein – emulsifier which incorporate air bubbles at interface and (3) pectin – polymer, by emulsification extraction method and to evaluate gastro retentive and controlled release properties at pH 4.0. The effects of various process variables on the particle size, % buoyancy and % drug entrapment were assessed by 32full factorial design and concluded by using two way ANOVA and polynomial regression methods. Process variables had considerable effect on all dependent variables. The microspheres were found to be regular in shape with rough surface. Microsphere formulation M9 showed particle size 59.60±0.95μm, buoyancy 82.0±0.27%, and %drug entrapment 97.54±0.53%. In vitro drug release study was done results calculated by PCP disso vi software revealed best fitted model for M9 as Korsmayer Peppas model and drug release in Fickian manner. In vitro cytotoxicity study on KATO III gastric cell line revealed methotrexate microspheres had greater cytotoxic effects on cell line in comparison to pure drug solution. In vivo gamma scintigraphy studies were done using albino mice showed more than 8 hrs retention in upper gastro intestinal tract