介孔材料MCM-41与推拉式渗透泵技术联合制备尼群地平口服片的研究

Study for Preparing the Oral Tablets of Nitrendipine by Nanometer Material MCM-41 in Combination with Push-pull Osmotic Pump Technology

目的利用纳米介孔材料MCM-41提高尼群地平溶解度,并结合推拉式渗透泵技术使药物达到控释释放。方法通过溶剂挥发法将药物尼群地平载入MCM-41的孔道中制备载药体系（NDP-MCM-41）,并且通过体外溶出试验优化最佳比例。利用差示扫描量热法,粉末X射线衍射法,和傅里叶红外光谱法对药物存在状态进行表征。通过体外溶出实验筛选渗透泵片剂最优处方。结果药物以无定形形式存在于载体孔道中,当药物与载体的比例为1∶5时,溶出效果最好。以PEO（10 000）作为助悬剂,PEO（600 000）作为助推剂采用直接压片法制备推拉式渗透泵。各个因素的用量,包衣增重的大小,打孔的大小都会影响药物的释放。结论纳米介孔材料MCM-41和推拉式渗透泵技术结合显著改善了尼群地平的溶出速率,避免了突释并且延长了药效。

OBJECTIVE Nano mesoporous material MCM-41 was used to improve the solubility of nitrendipine（NDP）, and combined with push-pull osmotic pump technology to achieve stable release of drugs. METHODS NDP was loaded into mesoporous pores by the solvent evaporation method to obtain the drug delivery system（NDP-MCM-41）. The optimal ratio was selected by the dissolution test in vitro. Differential Scanning Calorimetry（DSC）, Powder X-ray Diffraction（PXDR） and Fourier Transform Infrared Spectroscopy（FTIR） were used to characterize the existing state of NDP. The optimal formulation of osmotic pump tablets was obtained by in vitro dissolution test. RESULTS The drug presented at an amorphous form in mesoporous structure of MCM41. When the ratio of drug and carrier was 1∶5, the dissolution effect was the best. PEO（10 000） as a suspending agent and PEO（600 000） as a booster were used to prepare the push-pull osmotic pump by direct compression method. The amount of each factor, the weight of the coating and the size of the hole could affect the drug release. CONCLUSION The combination of nano mesoporous materials MCM-41 and push pull osmotic pump technology significantly improved the dissolution rate of nimodipine, avoided the burst release and prolonged the drug efficacy.