The Effects of Buffer Molarity, Agitation Rate, and Mesh Size on Verapamil Release from Modified-Release Mini-Tablets Using USP Apparatus 3

Abstract

Introduction In vitro dissolution testing is a critical component in the assessment of quality of a pharmaceutical product and for the validation of the development and manufacturing process of a product (1). Dissolution testing is also used to assess the rate at which a drug is released from a dosage form,as it provides a manufacturer with a rational basis on which to predict in vivo behaviour and dosage form optimisation (2). The granulation method used during manufacture may alter the rate of drug release from a formulation (3),as may the size,shape (4),and mechanical strength of a dosage form (5). Variables independent of dosage form design that may affect dissolution rates include temperature and pH of the dissolution media (3). The influence of temperature can be minimised in vitro by performing dissolution experiments at temperatures representative of the in vivo physiological conditions to which a dosage form would be exposed. In addition,agitation of the dissolution medium will influence the hydrodynamics of a test system,which in turn will affect the formation of a stagnant boundary layer, sink conditions,and consequently the rate of drug release from specific dosage forms (6,7). The purpose of these studies was to evaluate the effects of changing buffer molarity,agitation rate,and mesh/screen size on the release rate of a drug compound from sustainedrelease,hydrophilic matrix tablet formulations developed in our laboratory using USP Apparatus 3. Verapamil hydrochloride (VRP) was selected as a model drug,as it is well known and is widely used in the control of hypertension and angina.