Evaluation of Carbopol 71G for development of extended release dextromethorpahn tablets

MastersThere is an increasing interest in Carbopol polymers as gel matrix formers for extended release of drugs. Thus, it was the objective of this dissertation to evaluate the Carbopol 71G as extended release excipient in development of extended release matrix tablets of dextromethorphan hydrobromide using direct compression technique. The evaluation of Carbopol was carried out in comparison with the non-ionic polymer, hydroxypropyl methylcellulose (HPMC K15 M and HPMC 15) and the ionic polymer, methacrylic acid co-polymer (Eudragit L100-55) individually and in combination at different drug to polymer ratios. The effect of polymer concentration, polymers combination, compression force and storage conditions on the tablet physical properties, and drug release profile were evaluated on the manufactured tablets. The extended release formulations were compared to a marketed capsule product by applying the FDA dissolution recommended model independent f2 similarity test. Additionally, the mechanism of drug release from the extended release formulations were evaluated by applying different mathematical kinetic models on drug release profiles. It was found that the Carbopol polymer boost the tablet physical properties as investigated by crushing strength and friability test, indicating the good compressibility and binding characters of the investigated Carbopol polymer. A minimum concentration of 20% polymer was necessary to achieve a coherent matrix, able to extend the release of dextromethorphan. Increasing the concentration of Carbopol in the formulation leads to more retardation of drug release. A combination of Carbopol with other matrix forming excipients could modulate the release pattern of the drug, providing the formulator the great flexibility in achieving the desired drug release profiles. Drug release followed square root of time dependent kinetics, thus indicating a diffusion-controlled release mechanism. It was found that variation in compression force showed no significant change in release profile. This finding is considered a significant advantage for Carbopol formulations. On the other hand the Carbopol formulations showed reproducibility in the tablet physical properties and drug release profile. Therefore, a robust delivery system was attained using Carbopol polymer. A significant change in tablet physical properties was observed during stability test under accelerated storage conditions (40 ± 2 oC / 75 ± 5% RH) but no significant change in release profile up to 6 months. On the other hand, tablets stored under long term storage conditions (25 ± 2 oC / 60 ± 5% RH) showed no significant change in both tablet physical properties and release profile up to 12 months. It was concluded that Carbopol 71G is a good matrix forming excipient for the production of extended release matrix tablets. The combination of Carbopol and HPMC showed synergistic effect on the release of dextromethorphan thus, with this blend, it is possible to reduce the total amount of polymers in matrix and minimize the size and weight of the tablet