Kucera Shawn A, McGinity James W, Zheng Weijia, Shah Navnit H, Malick A Waseem, Infeld Martin H
Drug Dynamics Institute, College of Pharmacy, University of Texas at Austin, Austin, TX, USA.
Drug Dev Ind Pharm. 2007 Jul;33(7):717-26. doi: 10.1080/03639040601134165.
The objective of this study was to investigate the influence of two proteins, albumin and type B gelatin, on the physical aging of EUDRAGIT RS 30 D and RL 30 D coated theophylline pellets. The physicomechanical properties of sprayed films, thermal properties of cast films, influence of proteins on the zeta potential and particle size of the dispersion, and the release of proteins from cast films under simulated dissolution conditions were investigated. The release rate of theophylline decreased significantly over time from pellets coated with an acrylic dispersion containing 10% albumin when there was no acidification of the acrylic dispersion; however, when pellets were coated with an acidified EUDRAGIT/albumin dispersion, the theophylline release rate was stable for dosage forms stored in the absence of humidity. The drug release rate was faster for pellets coated with acrylic dispersions containing 10% gelatin compared to the albumin-containing formulations. When sprayed films were stored at 40 degrees C/75% RH, the water vapor permeability decreased significantly for both EUDRAGIT films and those containing EUDRAGIT and albumin; however, there was no significant change in this parameter when 10% gelatin was present. Albumin was released from the acrylic films when the pH of the dissolution media was below the isoelectric point of the protein while no quantitative release of gelatin was observed in pH 1.2 or 7.4 media. The effect of gelatin to prevent the decrease in drug release rate was due to stabilization in water vapor permeability of the film. Acidification of the polymeric dispersion resulted in electrostatic repulsive forces between albumin and the acrylic polymer, which stabilized the drug release rate when the dosage forms were stored in aluminum induction sealed containers at both 40 degrees C/75% RH and 25 degrees C/60% RH.
本研究的目的是考察两种蛋白质，即白蛋白和B型明胶，对包衣于EUDRAGIT RS 30 D和RL 30 D上的茶碱微丸物理老化的影响。研究了喷雾膜的物理机械性能、流延膜的热性能、蛋白质对分散体ζ电位和粒径的影响，以及在模拟溶出条件下流延膜中蛋白质的释放情况。当丙烯酸分散体未酸化时，含10%白蛋白的丙烯酸分散体包衣的微丸中茶碱的释放速率随时间显著降低；然而，当微丸用酸化的EUDRAGIT/白蛋白分散体包衣时，对于在无湿度条件下储存的剂型，茶碱释放速率是稳定的。与含白蛋白的制剂相比，含10%明胶的丙烯酸分散体包衣的微丸药物释放速率更快。当喷雾膜在40℃/75%相对湿度下储存时，EUDRAGIT膜以及含有EUDRAGIT和白蛋白的膜的水蒸气透过率均显著降低；然而，当存在10%明胶时，该参数无显著变化。当溶出介质的pH低于蛋白质的等电点时，白蛋白从丙烯酸膜中释放，而在pH 1.2或7.4介质中未观察到明胶的定量释放。明胶防止药物释放速率降低的作用归因于膜水蒸气透过率的稳定。聚合物分散体的酸化导致白蛋白与丙烯酸聚合物之间产生静电排斥力，当剂型在40℃/75%相对湿度和25℃/60%相对湿度下储存在铝箔感应密封容器中时，这使得药物释放速率得以稳定。
