目的 制备布林佐胺纳米晶体眼用原位凝胶，并考察其体外药物渗透性。方法 采用高压均质法制备布林佐胺纳米晶体。采用冷法制备布林佐胺纳米晶体眼用原位凝胶，使用中心复合设计对布林佐胺纳米晶体眼用原位凝胶的处方进行优化。利用Franz扩散池法考察布林佐胺纳米晶体眼用原位凝胶在羊眼角膜上的渗透性。结果 采用Soluplus作为稳定剂，其最佳质量浓度为5.0 mg/mL，制备的布林佐胺纳米晶体粒径分布、多分散性指数、Zeta电位和物理稳定性均较理想。原位凝胶剂的最佳处方配比为：羧甲基壳聚糖质量浓度为5.0 mg/mL，波洛沙姆407质量浓度为200.0 mg/mL，制备的布林佐胺纳米晶体眼用原位凝胶具有理想的黏度和凝胶化时间。布林佐胺纳米晶体眼用原位凝胶在羊眼角膜中的渗透滞后时间和渗透率均优于布林佐胺滴眼液。结论 制备的布林佐胺纳米晶体眼用原位凝胶处方合理，工艺可行，为布林佐胺的眼部给药提供一种更有效的途径。

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

湖北省卫生健康科研基金资助（WJ2021M218）