氯化钾渗透泵型控释片剂释药规律及机制的研究

 目的　研究渗透泵型控释片剂的释药规律及释药重现性,探索考察释药机制的新方法。方法　锅包衣方法制备渗透泵片。考察片心处方中的助悬剂、释药孔朝向、溶出仪转速、包衣膜厚度、包衣膜中PEG400用量、释药孔大小及片心硬度对释药的影响。测定一个释药孔制剂与两个释药孔制剂的药物释放度以考察释药机制。结果　释药孔朝向对不含助悬剂的制剂释药有明显影响,而对含助悬剂的制剂释药无影响。衣膜厚度增加,释药减慢,膜中PEG400含量增加,释药加快;而溶出仪转速、片剂释药孔大小及其片心硬度在一定范围内对释药没有显著影响。一个释药孔制剂与两个释药孔制剂的药物释放度基本一致。结论　在片心中加入助悬剂能显著提高制剂释药重现性。衣膜厚度、膜中PEG400含量是控制制剂释药速率的两大因素。比较一个释药孔与两个释药孔制剂的释放度是考察释放机制的快速有效方法。

Study on drug release and its mechanism of potassium chloride osmotic pump tablets

OBJECTIVE To improve the drug release reproducibility of elementary osmotic pump tablets and to investigate its drug release mechanism with a new method METHODS The KCl osmotic pump tablets were prepared with a single punch press and pan coating techniques The effective factors on the drug release, such as suspension agents in the tablet core, the direction and the diameter of drug release orifices, the rotation speed of dissolution testers, the thickness of coating film, PEG400 content in coating film and the hardness of tablet core, were investigated by dissolution tests The drug release of the tablets with one orifice or two orifices was determined, respectively RESULTS The direction of drug release orifices affected the release of tablets without suspension agent, but it had no effect on the tablets with suspension agent The rate of drug release increased with the decreasing of coating film thickness, or with the increasing of the PEG400 content in the coating film Other factors had little effects on the drug release The drug release behaviors of the tablets with one orifice were almost identical to those of the tablets with two orifices CONCLUSION It is essential to add suspension agents to tablet core in order to get good drug release reproducibility The thickness of the coating film and its PEG400 content are two main factors controlling drug release rate The dosage form mainly releases its drug with osmotic pressure mechanism The new method to investigate the drug release mechanism is convenient and practicable