目的 制备奈帕芬胺纳米混悬滴眼剂，并通过体外药物释放、渗透评价其质量。方法 通过单因素实验确定奈帕芬胺纳米混悬剂的处方组成和制备工艺；以卡波姆947P质量浓度、剪切速度、剪切时间作为自变量，以屈服应力和黏度作为评价指标，采用Box-Behnken实验设计优化奈帕芬胺纳米混悬滴眼剂的处方工艺。观察奈帕芬胺纳米混悬剂的微观形态、测定粒径，比较体外药物释放和离体角膜渗透性。结果 奈帕芬胺纳米混悬剂的最佳制备工艺为：泰洛沙泊的质量浓度为0.1 mg/mL，碾磨速度为2 500 r/min，碾磨时间为4 h。经Box-Behnken实验设计优化得到奈帕芬胺纳米混悬滴眼剂的最优处方为：卡波姆974P质量浓度为5.3 mg/mL，剪切速度为2 500 r/min，剪切时间为10 min。制备的奈帕芬胺纳米混悬剂的呈不规则状，部分粒子小于500 nm，平均粒径为（377.6±18.5）nm。与Nevanac^®的体外释药速率以及在羊眼角膜中的渗透率基本一致。结论 制备的奈帕芬胺纳米混悬滴眼剂各项指标与市售Nevanac^®无显著差别，为奈帕芬胺纳米混悬滴眼剂的仿制提供参考。

Objective To prepare Nepafenac Nanosuspension Eye Drops (Nep-NS-EDs) and evaluate its quality by in vitro drug release and permeability. Methods The formulation and preparation technology of Nepafenac Nanosuspension (Nep-NS) were determined by single factor test. The carbomer 947P concentration, shear rate, and shear time were taken as independent variables, and the yield stress and viscosity were taken as evaluation indexes. Box-Behnken test was used to optimize the formulation process of Nep-NS-EDs. The micromorphology of Nep-NS was investigated, and particle sizes were measured. The in vitro release rate and corneal permeability of Nep-NS-EDs were compared. Results The optimal preparation process of Nep-NS was as follows: the concentration was 1.0 mg/mL, milling speed was 2 500 r/min, and milling time was 4 h. The formulation process of Nep-NS-EDs was optimized by Box-Behnken design as follows: the concentration of carbomer 974P was 5.3 mg/mL, the shear speed was 2 500 r/min, and the shear time was 10 min. The prepared Nep-NS-EDs was irregular in shape, with some particles smaller than 500 nm. The average particle size was (377.6 ±18.5) nm. The in vitro release rate and permeability rate of Nep-NS-EDs were basically consistent with those of Nevanac^®. Conclusion The Nep-NS-EDs was prepared according to the optimized process parameters, and the product quality could be consistent with Nevanac^®. The indicators of the prepared Nep-NS-EDs had no significant difference with those of Nevanac^®, providing reference for the replication of Nep-NS-EDs.

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