Goole J, Vanderbist F, Amighi K
Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles, Campus de la Plaine, CP 207, Boulevard du Triomphe, Brussels 1050, Belgium.
Int J Pharm. 2007 Apr 4;334(1-2):35-41. doi: 10.1016/j.ijpharm.2006.10.018. Epub 2006 Oct 13.
This work relates to the development and the in vitro evaluation of sustained-release minitablets (MT), prepared by melt granulation and subsequent compression, which are designed to float over an extended period of time. Levodopa was used as a model drug. The importance of the composition and manufacturing parameters of the MT on their floating and dissolution properties was then examined. The investigation showed that MT composition and MT diameter had the greatest influence on drug release, which was sustained for more than 8h. By using the same formulation, the best floating properties were obtained with 3mm MT prepared at low compression forces ranging between 50 and 100N. Their resultant-weight (RW) values were always higher than those obtained with a marketed HBS dosage form within 13h. When they were filled into gelatin capsules, no sticking was observed. By evaluating the dissolution profiles of levodopa at different pH values, it was found that dissolution profiles depend more on the prolonged-release ability of Methocel K15M than on the pH-dependent solubility of levodopa. Finally, the robustness of the floating MT was assessed by testing the drug release variability in function of the stirring conditions during dissolution tests.
本研究涉及通过熔融制粒及后续压片制备的缓释微片（MT）的开发及体外评价，这些微片设计为能长时间漂浮。左旋多巴用作模型药物。随后研究了微片的组成和制造参数对其漂浮和溶出性能的重要性。研究表明，微片组成和微片直径对药物释放影响最大，药物释放可持续超过8小时。使用相同配方，在50至100N的低压力下制备的3mm微片具有最佳漂浮性能。其最终重量（RW）值在13小时内始终高于市售HBS剂型。当将它们填充到明胶胶囊中时，未观察到粘连现象。通过评估左旋多巴在不同pH值下的溶出曲线，发现溶出曲线更多地取决于甲基纤维素K15M的缓释能力，而非左旋多巴的pH依赖性溶解度。最后，通过测试溶出试验中搅拌条件对药物释放变异性的影响，评估了漂浮微片的稳健性。
