Alcohol-Induced Dose Dumping Studies in Gastro-Resistant Hard Gelatine Capsules Containing Immunosuppressant Drug

Abstract

Introduction: The purpose of this study is to evaluate the risk of alcohol-induced dose dumping of gastro-resistant hard gelatin capsules containing immunosuppressant drug used to medicate relapsing types of multiple sclerosis (MS). Such studies are essential to evaluate the rate change of drug release from the dosage form, if the patient took alcoholic beverages in daily life. According to the EMA guideline on the pharmacokinetic and clinical evaluation of modified release dosage forms, every altered release dosage form has to be evaluated for the hazard from alcohol induced dose dumping and / or changes in dissolution profiles (EMA/CHMP/QWP, 2014). Concerning these requirements, no differentiation is made between prolonged / sustained release products which normally contain larger doses (often double or more) as conventional immediate release (IR) forms and enteric coated preparations which should behave like IR products after dissolution of the functional coating and, thus, do not contain larger doses. Consequently, “instantaneous” release of the entire dose should not generate a risk for the patient. Nonetheless, impact of ethanol on drug release should also be investigated with these products. Results obtained from such tests should be carefully interpreted with respect to their therapeutic relevance.