目的 制備布林佐胺納米晶體眼用原位凝膠，并考察其體外藥物滲透性。方法 采用高壓均質法制備布林佐胺納米晶體。采用冷法制備布林佐胺納米晶體眼用原位凝膠，使用中心復合設計對布林佐胺納米晶體眼用原位凝膠的處方進行優(yōu)化。利用Franz擴散池法考察布林佐胺納米晶體眼用原位凝膠在羊眼角膜上的滲透性。結果 采用Soluplus作為穩(wěn)定劑，其最佳質量濃度為5.0 mg/mL，制備的布林佐胺納米晶體粒徑分布、多分散性指數、Zeta電位和物理穩(wěn)定性均較理想。原位凝膠劑的最佳處方配比為：羧甲基殼聚糖質量濃度為5.0 mg/mL，波洛沙姆407質量濃度為200.0 mg/mL，制備的布林佐胺納米晶體眼用原位凝膠具有理想的黏度和凝膠化時間。布林佐胺納米晶體眼用原位凝膠在羊眼角膜中的滲透滯后時間和滲透率均優(yōu)于布林佐胺滴眼液。結論 制備的布林佐胺納米晶體眼用原位凝膠處方合理，工藝可行，為布林佐胺的眼部給藥提供一種更有效的途徑。

Objective To prepare brinzolamide nanocrystals in situ gels and investigate its drug permeability in vitro .Methods Brinzolamide nanocrystals were prepared using high-pressure homogenization method. Brinzolamide nanocrystals in situ gels were prepared by cold method, and its formulation was optimized by central composite design. The permeability of brinzolamide nanocrystals in situ gels on the cornea of sheep eyes was investigated using Franz diffusion cell method.Results Using Soluplus as a stabilizer at optimized concentration of 5.0 mg/mL, the prepared brinzolamide nanocrystals in situ gels exhibited ideal particle size distribution, PDI, Zeta potential, and physical stability. The best prescription of brinzolamide nanocrystals in situ gels was Carboxymethyl chitosan concentration of 5.0 mg/mL and Poloxamer 407 concentration of 200.0 mg/mL. The prepared brinzolamide nanocrystals in situ gels exhibited ideal viscosity and gelation time. The lag time and permeability of brinzolamide nanocrystals in situ gels in sheep cornea were better than those of Brinzolamide Eye Drops.Conclusion The formulation of brinzolamide nanocrystals in situ gels is reasonable and the process is feasible, which provides a more effective way for the ophthalmic administration of brinzolamide.

R283

湖北省衛(wèi)生健康科研基金資助（WJ2021M218）