Bayomi Mohsen A, Abanumay Khalid A, Al-Angary Abdulaziz A
College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Int J Pharm. 2002 Aug 28;243(1-2):107-17. doi: 10.1016/s0378-5173(02)00263-6.
Nifedipine is a highly photosensitive drug that requires restricted protection from light during manufacturing, storage and handling of its dosage forms. Inclusion complexation of nifedipine with cyclodextrins (CDs) could be advantageous in protecting the drug against the effect of light. In this study, solid inclusion complexes of nifedipine with beta-cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and dimethyl-beta-cyclodextrin (DM-beta-CD) were prepared using the coprecipitation method. The obtained solid inclusion complexes have been confirmed by differential scanning calorimetry (DSC), X-ray diffraction and infrared spectroscopy (IR). The IR spectra indicated partial inclusion of nifedipine molecules into CD cavities through the dihydropyridine ring. Inclusion complexation was also associated with a dramatic enhancement of drug dissolution with magnitudes depended on the type of CD. The effect of exposure to fluorescent lamp and sunlight on the photodegradation of uncomplexed and complexed nifedipine was tested. Photodegradation of nifedipine was monitored using a high performance liquid chromatographic (HPLC) assay method. Inclusion complexation of nifedipine showed to retard drug photodegradation as indicated by degradation rate constant lowering with values depended on light source and type of complexing agent. This effect was the least with beta-CD compared with that of modified beta-CD. It was also interesting to notice that inclusion complexation of nifedipine offered much higher protection against the effect of fluorescent lamp than that of sunlight. The obtained results suggests that the design of solid dosage forms of nifedipine such as a fast dissolving nifedipine tablets is possible with the advantages of low required light protection.
硝苯地平是一种对光高度敏感的药物，在其剂型的生产、储存和处理过程中需要严格避光保护。硝苯地平与环糊精（CDs）形成包合物可能有利于保护药物免受光的影响。在本研究中，采用共沉淀法制备了硝苯地平与β-环糊精（β-CD）、羟丙基-β-环糊精（HP-β-CD）和二甲基-β-环糊精（DM-β-CD）的固体包合物。通过差示扫描量热法（DSC）、X射线衍射和红外光谱（IR）对所得固体包合物进行了确认。红外光谱表明硝苯地平分子通过二氢吡啶环部分包合进入CD空腔。包合作用还与药物溶出度的显著提高有关，溶出度的大小取决于CD的类型。测试了荧光灯和阳光照射对未包合和包合硝苯地平光降解的影响。采用高效液相色谱（HPLC）测定法监测硝苯地平的光降解。硝苯地平的包合作用显示出能延缓药物光降解，降解速率常数降低，其值取决于光源和络合剂类型。与改性β-CD相比，β-CD的这种效果最小。还值得注意的是，硝苯地平的包合作用对荧光灯的防护作用比对阳光的防护作用高得多。所得结果表明，设计硝苯地平的固体剂型，如速溶硝苯地平片是可行的，且具有低避光要求的优点。
