Maria Doaa Nabih, Abd-Elgawad Abd-Elgawad Helmy, Soliman Osama Abd-Elazeem, El-Dahan Marwa Salah, Jablonski Monica M
Department of Ophthalmology, Hamilton Eye Institute, The University of Tennessee Health Science Center, 930 Madison Avenue, Suite 731, Memphis, Tennessee, 38163, USA.
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Pharm Res. 2017 Apr;34(4):809-824. doi: 10.1007/s11095-017-2110-x. Epub 2017 Feb 2.
Preparation and evaluation of topical ophthalmic formulations containing nimodipine-CD complexes prepared using HP-β-CD, SBE-β-CD and M-β-CD for the management of glaucoma.
Nimodipine-CD complexes were prepared using a freeze-drying method. Two different molar ratios (NMD:CD) were used for each cyclodextrin. The inclusion complexes were characterized using DSC, FTIR, yield (%), drug content and in vitro release characteristics. NMD-CD complexes incorporated into chitosan eye drops and a temperature-triggered in situ gelling system were evaluated for their pH, viscosity and in vitro release characteristics. We determined the intraocular pressure (IOP) lowering effect of NMD-hydroxypropylmethylcellulose (HPMC) eye drops through a single dose response design using C57BL/6J mice. The minimum effective concentration (MEC) of nimodipine was further applied to mice that vary in the parental allele of Cacna1s, the drug target of nimodipine. Cytotoxicity was also evaluated.
Our ophthalmic formulations possessed pH and viscosity values that are compatible with the eye. In vitro release of nimodipine was significantly increased from chitosan eye drops containing NMD-CD complexes compared to uncomplexed drug. Administration of nimodipine can lower IOP significantly after a single drop of drug HPMC suspension. The IOP-lowering response of the MEC (0.6%) was significantly influenced by the parental allele of Cacna1s.
Nimodipine can be used as a promising topical drug for management of glaucoma through ocular delivery.
制备并评估含尼莫地平 - 环糊精复合物的局部眼用制剂，该复合物采用羟丙基 - β - 环糊精（HP - β - CD）、磺丁基 - β - 环糊精（SBE - β - CD）和甲基化 - β - 环糊精（M - β - CD）制备，用于青光眼的治疗。
采用冷冻干燥法制备尼莫地平 - 环糊精复合物。每种环糊精使用两种不同的摩尔比（NMD:CD）。通过差示扫描量热法（DSC）、傅里叶变换红外光谱法（FTIR）、产率（%）、药物含量和体外释放特性对包合物进行表征。对掺入壳聚糖滴眼液和温度触发原位凝胶系统中的NMD - CD复合物进行pH值、粘度和体外释放特性评估。我们通过单剂量反应设计，使用C57BL/6J小鼠确定了尼莫地平 - 羟丙基甲基纤维素（HPMC）滴眼液的降眼压效果。将尼莫地平的最低有效浓度（MEC）进一步应用于尼莫地平药物靶点Cacna1s亲本等位基因不同的小鼠。还评估了细胞毒性。
我们的眼用制剂的pH值和粘度值与眼睛相容。与未复合的药物相比，含NMD - CD复合物的壳聚糖滴眼液中尼莫地平的体外释放显著增加。单次滴注药物HPMC混悬液后，尼莫地平给药可显著降低眼压。MEC（0.6%）的降眼压反应受Cacna1s亲本等位基因的显著影响。
尼莫地平可作为一种有前景的局部用药，通过眼部给药用于青光眼的治疗。
