目的 制備奈帕芬胺納米混懸滴眼劑，并通過(guò)體外藥物釋放、滲透評(píng)價(jià)其質(zhì)量。方法 通過(guò)單因素實(shí)驗(yàn)確定奈帕芬胺納米混懸劑的處方組成和制備工藝；以卡波姆947P質(zhì)量濃度、剪切速度、剪切時(shí)間作為自變量，以屈服應(yīng)力和黏度作為評(píng)價(jià)指標(biāo)，采用Box-Behnken實(shí)驗(yàn)設(shè)計(jì)優(yōu)化奈帕芬胺納米混懸滴眼劑的處方工藝。觀察奈帕芬胺納米混懸劑的微觀形態(tài)、測(cè)定粒徑，比較體外藥物釋放和離體角膜滲透性。結(jié)果 奈帕芬胺納米混懸劑的最佳制備工藝為：泰洛沙泊的質(zhì)量濃度為0.1 mg/mL，碾磨速度為2 500 r/min，碾磨時(shí)間為4 h。經(jīng)Box-Behnken實(shí)驗(yàn)設(shè)計(jì)優(yōu)化得到奈帕芬胺納米混懸滴眼劑的最優(yōu)處方為：卡波姆974P質(zhì)量濃度為5.3 mg/mL，剪切速度為2 500 r/min，剪切時(shí)間為10 min。制備的奈帕芬胺納米混懸劑的呈不規(guī)則狀，部分粒子小于500 nm，平均粒徑為（377.6±18.5）nm。與Nevanac^®的體外釋藥速率以及在羊眼角膜中的滲透率基本一致。結(jié)論 制備的奈帕芬胺納米混懸滴眼劑各項(xiàng)指標(biāo)與市售Nevanac^®無(wú)顯著差別，為奈帕芬胺納米混懸滴眼劑的仿制提供參考。

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.

R944