Drug Transport Mechanisms from Carbopol/Eudragit Verapamil Sustained-Release Tablets

The objectives of this study were to compare dissolution profiles of a verapamil (VRP) formulation manufactured inhouse and Isoptin SR using USP Apparatus 2 and 3 and to elucidate drug release kinetics of these dosage forms. Eudragit NE 30D (ethyl acrylate–methyl methacrylate copolymer in a 2:1 ratio) aqueous dispersion was used as a granulating binder for the manufacture of VRP mini-matrix sustained-release tablets. The wet granulation process was performed to prepare free-flowing granules that were blended with Carbopol. The tablets were manufactured using a single-punch press by compression of the granules with magnesium stearate as a lubricant. Drug release was determined in phosphate buffer solution using USP Apparatus 2 and 3. Dissolution data were fitted to zeroand first-order models; in addition, the kinetic data were determined by evaluation of Higuchi release kinetics. The mechanism of drug release was established using the Korsmeyer–Peppas model. In general, all tablets showed high mechanical resistance with less than 1% friability. There was no significant difference between the dissolution profiles of the formulation manufactured in-house and the commercially available product. The release mechanism of the formulated and marketed products was controlled by anomalous non-Fickian diffusion. VRP release was prolonged for 12 h indicating the usefulness of the formulation as a twice-daily dosage form. The mechanism of drug release for the dosage forms was unaffected by the choice of apparatus. INTRODUCTION Since the adoption of dissolution testing, pharmaceutical scientists have naturally performed comparisons of dissolution profiles. Many of the methods of comparison have often been qualitative or semiquantitative and have often relied on the technological skill and learned art of the pharmaceutical scientist. While these qualitative assessments of the degree of dissolution profile similarity have been useful, regulatory agencies have required more objective and quantitative methods to compare dissolution profiles for regulatory purposes (1). In addition, mathematical modeling of drug-release profiles from controlled drug delivery devices has been used to provide knowledge relating to mass-transport mechanisms involved in the control of drug release from dosage forms (2). Of the various mechanisms that control drug release, the most important are diffusion, watertriggered transport (swelling) coupled with chain relaxation, and slow erosion of polymer (2–5). However, the occurrence of multicomponent transport processes, different types of matrices, composition, device geometries, drug loading and saturation solubility in the matrix, diffusion, swelling, polymer dissolution, and erosion may complicate the analysis of drug release from controlledrelease delivery systems (6). Furthermore, mathematical approaches covering all possible chemical and physical processes are not yet available; hence, to describe drug release, there is a need to identify or develop an adequate mathematical theory for specific types of drug delivery systems (2). It is recognized that alternative approaches have been reported; these should be considered and used in combination with conventional methods of analysis that have already been established (6). These new techniques include the use, for example, of artificial neural network (ANN) methodology to predict drug-release profiles from drug delivery systems (6, 7) using popular drug carrier materials. There is a paucity of information pertaining to the transport mechanism and release kinetics of drugs from dosage forms that contain both Eudragit NE 30D and Carbopol 794P NF. The authors (5) investigated the swelling and erosion behavior of VRP from sustainedrelease tablets based on the theory of macromolecular disentanglement. Their results showed that swelling and erosion behavior dictate the kinetics and mechanism of drug release from sustained-release formulations, but one process may predominate over the other because of different polymer characteristics. VRP, a calcium-channel blocker that limits calcium ion entry into cells, is widely used in the management of angina, supraventricular arrhythmias, and hypertension (8). The objective of this investigation was to compare the dissolution profiles of a VRP formulation manufactured in our laboratory to those for Isoptin SR to elucidate the release kinetics when using USP Apparatus 2 and 3. In this study Eudragit NE 30D, a neutral milky-white aqueous dispersion of low viscosity and characteristic aromatic odor consisting of polymethacrylic acid esters (9), was used as the granulating agent. Traditionally this material has been used as an aqueous coating agent. *Corresponding author. diss-18-03-04.indd 30 8/31/2011 1:30:56 PM dx.doi.org/10.14227/DT180311P30