Diclofenac-induced Gastric Ulceration in Rats: Protective Roles of Pantoprazole and Misoprostol
E. E. Zien El-Deen *
Department of Pharm. Technology and Pharmacology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
N. A. El-Mahdy
Department of Pharm. Technology and Pharmacology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
M. A. El Rashidy
Department of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt
M. M. Ghorab
Department of Pharmaceutics, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
Shadeed Gad
Department of Pharmaceutics, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
H. A. Yassin
Department of Pharmaceutics, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
*Author to whom correspondence should be addressed.
Abstract
Gastrointestinal damage caused by diclofenac remains a significant clinical problem. Pantoprazole provides potent and long-lasting inhibition of gastric acid secretion and has proven efficacy in healing diclofenac-associated ulcers, including those with continued exposure to diclofenac. The objective of this study was to prepare and evaluate microbeads of diclofenac sodium coated with sodium alginate and Hydroxypropylmethylcellulose (HPMC) in order to obtain controlled release drug delivery system. The ulcerogenic activity and histopathological effects of the prepared formulation were compared with a marked formula containing the drug with misoprostol which orally administered to male Wistar rats. Ionotropic gelation technique was the technique of choice to encapsulate the drug. IR spectral analysis indicated no interaction between the drug and polymers used. Microbeads which showed a significant reduction in the release of diclofenac at acidic pH of the stomach as well as maximal release at alkaline pH of the intestine were selected to conduct further in vivo evaluation. The beads were administered to rats in combination with pantoprazole. The obtained ulcer index as well as the histopathological effects of the proposed formulations was compared to marketed formula containing the drug combined with misoprostol. The obtained In vivo results indicate that administration of pantoprazole and diclofenac microbeads has shown efficacy in reducing the risk of GIT ulcerations compared with administration of misoprostol and diclofenac or diclofenac separately.
Keywords: Diclofenac sodium, microbeads, ionotropic gelation technique, ulcerogenic effect of diclofenac, controlled release system, pantoprazole, misoprostol