Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, IS-107 Reykjavik, Iceland.
J Pharm Pharm Sci. 2010;13(3):336-50. doi: 10.18433/j3m88b.
Study the complexation of dexamethasone in combinations of γ-cyclodextrin (γCD) and 2-hydroxypropyl-γ-cyclodextrin (HPγCD) with emphasis on solid characterization and development of aqueous dexamethasone eye drop suspension for drug delivery through sclera.
Dexamethasone/cyclodextrin (dexamethasone/CD) solid complex systems were prepared and characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and by in vitro drug dissolution testing. Sample eye drop suspensions were prepared applying solubilizer/suspender consisting of γCD/HPγCD mixtures, poloxamer 407 (P407) and polyvinylpyrrolidone. The eye drop suspension was characterized by its physicochemical properties.
The solid characterization techniques applied suggested that solid complexes were being formed. The results indicated that dexamethasone formed non-inclusion or micelle-like aggregates with HPγCD and the γCD/HPγCD mixture. The dissolution and dexamethasone release from the solid dexamethasone/γCD/HPγCD complexes was much faster than from the solid dexamethasone/γCD and dexamethasone/HPγCD complexes. The diameter of the solid particles in the dexamethasone eye drop suspension formulations were in all cases less than 10 μm with a mean diameter from 2.5 to 5.8 μm. The particle size decreased with increasing amount of P407. Permeation studies through semipermeable membrane and porcine sclera showed that increasing the amount HPγCD could enhance drug transport through the membrane barriers and this was related to enhanced drug solubility. The permeation rates were, however, decreased compared to formulation containing γCD alone due to larger hydrodynamic diameter of dexamethasone/γCD/HPγCD complex aggregates. All formulations were both chemically stable for at least 8 months at 25°C and 40°C.
Combination of γCD and HPγCD, i.e., formation of dexamethasone/γCD/HPγCD complexes, resulted in synergistic effect. That is the mixture had greater solubilizing effect than the individual CD, resulted in enhanced dissolution and drug delivery through membranes. Furthermore, it is possible to control the drug release rate by adjusting the γCD:HPγCD ratio in the solid dexamethasone/γCD/HPγCD complexes.
研究地塞米松与γ-环糊精（γCD）和 2-羟丙基-γ-环糊精（HPγCD）组合的络合作用，重点研究通过巩膜给药的地塞米松眼用混悬液的固体特性和开发。
制备地塞米松/环糊精（地塞米松/CD）固体配合物系统，并通过傅里叶变换红外光谱（FT-IR）、差示扫描量热法（DSC）、X 射线衍射（XRD）和体外药物溶出度试验进行表征。应用由 γCD/HPγCD 混合物、泊洛沙姆 407（P407）和聚乙烯吡咯烷酮组成的溶媒/混悬剂制备样品眼用混悬剂。通过其物理化学性质对眼用混悬剂进行表征。
应用的固体特性技术表明形成了固体配合物。结果表明，地塞米松与 HPγCD 和 γCD/HPγCD 混合物形成非包合或胶束样聚集体。与固体地塞米松/γCD 和地塞米松/HPγCD 配合物相比，固体地塞米松/γCD/HPγCD 配合物的溶出度和地塞米松释放速度更快。地塞米松滴眼混悬剂制剂中固体颗粒的直径均小于 10μm，平均直径为 2.5 至 5.8μm。随着 P407 用量的增加，粒径减小。通过半透膜和猪巩膜的渗透研究表明，增加 HPγCD 的量可以增强药物通过膜屏障的运输，这与药物溶解度的增强有关。然而，与仅含 γCD 的制剂相比，由于地塞米松/γCD/HPγCD 配合物聚集体的水动力直径较大，渗透速率降低。所有制剂在 25°C 和 40°C 下至少 8 个月均保持化学稳定。
γCD 和 HPγCD 的组合，即地塞米松/γCD/HPγCD 配合物的形成，产生协同作用。即混合物具有比单独的 CD 更大的增溶作用，导致通过膜的溶解和药物递送增强。此外，可以通过调整固体地塞米松/γCD/HPγCD 配合物中 γCD:HPγCD 的比例来控制药物释放速率。
