目的 根皮素（PT）為難溶性藥物，且口服相對(duì)生物利用度低，通過與纈沙坦（VST）制備成共非晶（CA）提高其溶出速率，從而提高其口服相對(duì)生物利用度。方法 以VST為藥物載體，PT為模型藥物，采用噴霧干燥法制備CA。傅里葉紅外圖譜（FT-IR）觀察樣品的官能團(tuán)結(jié)構(gòu)及分子間相互作用力；差示掃描量熱法（DSC）測(cè)定玻璃化轉(zhuǎn)變溫度（T_g）進(jìn)一步驗(yàn)證PT和VST分子間的相互作用力；粉末X-射線衍射（PXRD）觀察晶體學(xué)特性；掃描電子顯微鏡（SEM）觀察樣品的微觀結(jié)構(gòu)。考察藥物在模擬胃液、模擬腸液中的本征溶出，計(jì)算溶出速率（IDR）；考察CA在高溫、不同濕度下的穩(wěn)定性；考察CA、PT（200 mg·kg^-1）在大鼠體內(nèi)藥動(dòng)學(xué)。結(jié)果 FT-IR和DSC表明CA中PT與VST有較強(qiáng)的分子之間相互作用力，PXRD和SEM證明CA為無定形態(tài)，表明PT與VST共噴霧形成了共非晶；CA本征溶出結(jié)果表明相較于PT，CA溶出速率有明顯提升（P＜0.05）；CA大鼠體內(nèi)口服相對(duì)生物利用度相較原料藥提高4.12倍，C_max提高7.44倍。CA在高溫條件（50±2）℃表現(xiàn)出良好的穩(wěn)定性，但濕穩(wěn)定性較差。結(jié)論 PT與VST成功制備成CA，明顯的改善了PT的溶出及口服相對(duì)生物利用度，并且有較好的熱穩(wěn)定性。

Objective Phloretin (PT) is an insoluble drug with low oral bioavailability.It is proposed to improve its dissolution rate by preparing co-amorphous (CA) with valsartan (VST), so as to improve its oral bioavailability. Methods CA was prepared by spray drying method with VST as drug carrier and PT as model drug. Fourier infrared spectroscopy (FT-IR) was used to observe the structure of functional groups and the intermolecular forces of the samples. The glass transition temperature (T_g) was determined by differential scanning calorimetry (DSC) to further verify the interaction between PT and VST molecules. The crystallographic properties of powder were observed by X-ray diffraction (PXRD). The microstructure of the sample was observed by scanning electron microscopy (SEM). Investigate the intrinsic dissolution of drugs in simulated gastric and intestinal fluids, and calculate the dissolution rate (IDR); Assess the stability of CA under high temperature and different humidity conditions; Investigating the pharmacokinetics of CA and PT (200 mg·kg^-1) in rats. Results FT-IR and DSC show that there is a strong interaction force between PT and VST in CA, and PXRD and SEM show that CA is amorphous, indicating that PT and VST are co-sprayed to form eutectic amorphous. The dissolution rate of CA is significantly higher than that of PT (P < 0.05). The oral bioavailability in vivo was 4.12 times higher than that of the bulk drug, and the C_max was 7.44 times higher. CA showed good stability at high temperature (50±2)℃ , but poor wet stability. Conclusion The CA prepared by PT and VST can obviously improve the dissolution rate and oral bioavailability of PT, and has good thermal stability.

R943

2024年中央引導(dǎo)地方科技發(fā)展資金計(jì)劃項(xiàng)目(2024ZY002);青海省基礎(chǔ)研究計(jì)劃項(xiàng)目(2022-ZJ-748)