目的 分別采用4種載體制備蛇床子素固體分散體（osthole solid dispersions，Ost-SDs），旨在調(diào)控蛇床子素口服后釋放部位和釋放度。方法 分別以醋酸羥丙甲基纖維素琥珀酸酯（hydroxypropyl methylcellulose acetate succinate，HPMCAS，H、M、L型）和尤特奇L100（Eudragit L100，EL100）為載體，采用溶劑蒸發(fā)法制備Ost-SDs，以在0.1 mol/L鹽酸水溶液和pH 6.8磷酸鹽緩沖液（PBS）中的累積溶出率為考察指標，篩選Ost-SDs藥載比，確定最優(yōu)處方；分別采用掃描電子顯微鏡（scanning electron microscope，SEM）、傅里葉變換紅外光譜（Fourier transform infrared spectroscopy，F(xiàn)TIR）、X射線粉末衍射分析（X-ray powder diffraction analysis，XRD）、差示掃描量熱分析（differential scanning calorimetry，DSC）和偏振光顯微鏡（polarized light microscopy，PLM）等方法表征其形貌和物理化學(xué)性質(zhì)；通過進行水接觸角、平衡溶解度和體外釋放試驗，評價Ost-SDs的體外水溶性。結(jié)果Ost-SDs的優(yōu)選處方為以無水乙醇-二氯甲烷（1∶1）混合溶液為溶劑，蛇床子素質(zhì)量濃度為0.6 mg/mL，藥載比為1∶7；在4種載體制備的Ost-SDs中，蛇床子素的晶型均為無定型；Ost-SDs的FTIR圖表明蛇床子素和載體之間能夠形成分子間氫鍵；蛇床子素原料藥和物理混合物（Ost-PMs）中的蛇床子素，在PLM下均能夠觀察到明顯的雙折射現(xiàn)象，而在Ost-SDs中，蛇床子素基本沒有雙折射現(xiàn)象；Ost-SDs的水接觸角低于Ost-PMs，表明其水潤濕性增強；Ost-SDs在pH 6.8 PBS中的溶解度是蛇床子素原料藥的156%～193%；而且Ost-SDs在含有0.1%聚山梨酯80的鹽酸水溶液中，蛇床子素在2 h的累積釋放率低于Ost-PMs，而在pH 6.8 PBS中，其累積釋放度高于Ost-PMs。結(jié)論 以HPMCAS（H、M、L型）和EL100為載體，采用溶劑蒸發(fā)法能夠成功制備Ost-SDs，而且4種Ost-SDs均能夠保證蛇床子素在模擬胃液中少量釋放，同時提高蛇床子素在模擬小腸液中的釋放速率和累積釋放率。

Objective A total of four carriers were used to prepare osthole solid dispersions (Ost-SDs), aiming to regulate the release site and release rate after oral administration of osthole. Methods The Ost-SDs were prepared by solvent evaporation method using hydroxypropyl methylcellulose acetate succinate (HPMCAS, H, M and L) and Eudragit L100 (EL100) as carriers, respectively; and the drug-loading ratio was screened and the optimal prescription was determined using the accumulated dissolution rate in 0.1 mol/L aqueous hydrochloric acid and pH 6.8 phosphate buffer solution (PBS) as the index; the morphology and physicochemical properties of Ost-SDs were characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction analysis (XRD), differential scanning calorimetry (DSC) and polarized light microscopy (PLM); and the water solubility of the Ost-SDs was evaluated by performing aqueous contact angle, equilibrium solubility, and in vitro release tests. Results The optimum formulation of Ost-SDs was as follow: the mixture solution of anhydrous ethanol-dichloromethane (1:1) as solvent, osthole concentration of 0.6 mg/mL, and drug-loading ratio of 1:7; the crystalline form of osthole was amorphous in the Ost-SDs prepared in the study; and FTIR of the Ost-SDs demonstrated that intermolecular hydrogen bonding could be formed between the osthole and the carrier; both crude osthole and the physical mixtures (Ost-PMs) were observed obvious birefringence phenomenon under PLM, while Ost-SDs were basically free of birefringence phenomenon; the water contact angle of Ost-SDs was lower than that of the Ost-PMs, which indicated its enhanced water wettability; in comparison with crude osthole, the solubility of Ost-SDs in pH 6.8 PBS was 156% to 193%; and the accumulated dissolution rate of osthole of Ost-SDs at 2 h was lower than that of Ost-PMs in aqueous hydrochloric acid solution containing 0.1% Tween 80, but higher than that of Ost-PMs in pH 6.8 PBS. Conclusion The solvent evaporation method was able to successfully prepare Ost-SDs using HPMCAS (H, M, L types) and EL100 as carriers, and all the four Ost-SDs prepared in the study reduced the dissolution of osthole in simulated gastric fluid and improve the dissolution rate and cumulative dissolution rate of osthole in simulated small intestinal fluid.

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河北省自然科學(xué)基金資助（H2022406073）；河北省高等學(xué)?？茖W(xué)技術(shù)研究項目資助（ZD2020154）；河北省中央引導(dǎo)地方科技發(fā)展資金項目（246Z2504G）；河北?。ǔ械拢┲兴幉漠a(chǎn)業(yè)技術(shù)研究院開放性課題資助；承德醫(yī)學(xué)院中藥學(xué)學(xué)科建設(shè)項目