Stithit S, Chen W, Price J C
R&D Department, Siam Pharmaceutical Co. Ltd., Bangkok, Thailand.
J Microencapsul. 1998 Nov-Dec;15(6):725-37. doi: 10.3109/02652049809008255.
The objective of this study was to prepare floating theophylline microspheres with zero order release profiles for use as buoyant reservoirs with increased retention time in the stomach. The microspheres were prepared by a modified emulsion-solvent evaporation method using a polymer mixture of cellulose acetate butyrate and Eudragit RL 100 (1:1). The drug-polymer dispersions were pressurized under carbon dioxide gas which dissolved in the drug-polymer dispersions and formed bubbles upon the release of the pressure. Some of the bubbles were entrapped in the dispersed drug-polymer droplets and eventually formed internal cavities in the microspheres. The resulting microspheres were characterized for size distribution, morphology, density, drug-polymer content, buoyant capacity and drug release behaviour. The microspheres were spherical with relatively smooth surfaces with round hollow cavities. The microspheres and low densities (less than 1 g/cm3) and remained floating for more than 24 h in pH 1.2 and 7.5 buffers. The dissolution profiles of the floating theophylline microspheres showed near zero order kinetics and sustained release in both pH 1.2 and 7.5 buffers. Modified microspheres processed with the addition of 2% w/v polysorbate 80 to the internal phase had smaller sizes, lower densities and faster drug release compared with those without the addition of the surfactant.
本研究的目的是制备具有零级释放曲线的茶碱漂浮微球，用作在胃中滞留时间延长的漂浮贮库。微球通过改良的乳液 - 溶剂蒸发法制备，使用醋酸丁酸纤维素和丙烯酸树脂RL 100（1:1）的聚合物混合物。药物 - 聚合物分散体在二氧化碳气体压力下进行处理，二氧化碳溶解在药物 - 聚合物分散体中，压力释放时形成气泡。一些气泡被困在分散的药物 - 聚合物液滴中，最终在微球中形成内部空腔。对所得微球的粒径分布、形态、密度、药物 - 聚合物含量、漂浮能力和药物释放行为进行了表征。微球呈球形，表面相对光滑，有圆形中空腔。微球密度较低（小于1 g/cm³），在pH 1.2和7.5缓冲液中可漂浮超过24小时。茶碱漂浮微球的溶出曲线在pH 1.2和7.5缓冲液中均显示出近似零级动力学和缓释特性。与未添加表面活性剂的微球相比，在内相中添加2% w/v聚山梨酯80处理的改良微球尺寸更小、密度更低且药物释放更快。
