Drug and Excipient Compatilbility Study of Selected Proton Pump Inhibitors

Abstract

The study of drug–excipient’s compatibility represents an important phase in the preformulation stage for the development of all dosage forms. Potential physical and chemical interactions between drugs and excipients can affect the chemical nature, the stability and bioavailability of drugs and their therapeutic efficacy and safety. The class of drugs selected for drug and excipient compatibility study is Proton Pump Inhibitors (PPIs) these agents selectively and irrevocably inhibit the gastric hydrogen/potassium adenosine tri phosphatase (H+/K+-exchanging ATPase), part of the ‘proton pump’ that makes the final step in the acid secretory process. They inhibit both basal and stimulated secretion of gastric acid, exclusively of the nature of parietal cell stimulation. Esomeprazole magnesium and pantoprazole sodium were selected to check drug and excipient compatibility study of Proton Pump Inhibitors (PPIs). According to literature review PPIs get degraded in very mild oxidative stress condition another conclusion was found that polyvinylpyrrolidone contains organic peroxide as an impurity in it which is more reactive than hydrogen peroxide. Although PVP is widely used as a binder in the tablet formulation of PPIs. The aim of the present study was to identify the compatibility of selected proton pump inhibitors with different grades of Polyvinylpyrrolidone i.e. PVP K30 and PVP K90. Accelerated stability study was carried out in accordance with ICH guidelines for drug alone as well as binary mixtures of drug and excipients. Impurities generated were well separated by the chromatographic conditions of esomeprazole magnesium and pantoprazole sodium related substances given in Indian Pharmacopoeia. Compatibility of drug and excipient was checked by two analytical methods High Performace Liquid chromatography (HPLC) and Differential Scanning Calorimetry (DSC). Results obtained were supporting the hypothesis. Impurities generated was beyond the identification threshold specified in ICH Q3A (R1) so it can further be qualified and characterized by suitable analytical techniques.