Abstract

GENERATION AND CHARACTERIZATION OF NOVEL DELAYED EXTENDED RELEASE CO-PROCESSED EXCIPIENT WITH GASTRIC STABILIZING ACTIVITY

Prashant Kumar Chaudhari*, H. K. Jain, P. Sharma and B. Srivastava

ABSTRACT

The objective of present study was to develop co-processed pharmaceutically elegant pH dependent polymer for highly unstable model drug in acidic environment as a stable delayed and sustained release tablet formulation. Omeprazole is a specific and non-competitive inhibitor of the enzyme H+/K+-ATPase. It is chronically used in patients suffering from peptic ulcer, duodenal ulcer etc. It is unstable in conditions of low pH and required protection from the effects of gastric acid when given orally so it is formulated in the form of delayed release tablet dosage forms utilising co-processed polymers. Directly compressible (DC) co-processed excipient capable of providing delayed and sustained release with improved functionality was developed without any chemical modification by employing various techniques such as physical mixing, high shear mixer granulation and spray drying. Co-processed excipient was developed by using pH dependent polymer Eudragit L100, separately, in combination with different concentration of hydroxyl propyl methyl cellulose 100 cps (Methocel K100 LV, HPMC), ethyl cellulose (Ethocel N50, EC) and hydroxyl propyl cellulose (Klucel EF, HPC). All co-processed excipients were evaluated for their properties like bulk density, tapped density and particle size determination (PSD). Out of eighteen combinations, the nine co-processed excipients exhibited promising flow properties were found suitable for direct compression and formulated as tablets. Omeprazole was selected as a model drug and the formulation was developed employing direct compression approach. The developed tablets were evaluated for physical parameters like uniformity of weight, thickness, hardness, friability and assay. Disintegration and acid resistant test confirmed that some batches could resist acidic pH for 2 hrs. In vitro dissolution study confirms that formulation prepared using co-processed excipient showed sustained drug release. The optimised tablet formulation was characterised by DSC, PXRD and FTIR which confirms the absence of any chemical change during co-processing. In- vivo pharmacokinetic study of optimised formulation in rats showed sustained plasma drug levels as compared with the marketed formulation. The optimised formulation was kept for stability study for six months as per ICH guidelines and found to be stable. Study revealed that co-processed excipient has advantage over polymers with single property and can be utilised for delayed and sustained release formulation.

Keywords: Omeprazole, Direct compression, Eudragit L100, Ethylcellulose, Delayed release, Sustained release.