目的 制備阿苯達(dá)唑（ABZ）-鹽酸（HCl）鹽（ABZ-HCl），并對(duì)鹽的固態(tài)性質(zhì)、體外溶出行為、穩(wěn)定性和生物利用度進(jìn)行評(píng)價(jià)。方法 溶劑蒸發(fā)法制備結(jié)晶的ABZ-HCl，使用核磁共振氫譜（¹H-NMR）對(duì)制備的ABZ-HCl進(jìn)行驗(yàn)證，通過(guò)粉末X射線衍射（PXRD）、動(dòng)態(tài)水吸附（DVS）、熱重分析（TGA）和差示掃描量熱法（DSC）進(jìn)行固態(tài)性質(zhì)的表征；對(duì)藥物鹽進(jìn)行表觀溶解度和固有溶出速率（IDR）的測(cè)定以觀察其在不同pH條件下溶解度和溶出速率；進(jìn)行了ABZ-HCl在強(qiáng)光照射（4 500±500 lx）、高濕（92.5%±5% RH）和高溫條件（50±2）℃，以及加速試驗(yàn)條件（40℃、75%±5% RH）的穩(wěn)定性研究；評(píng)價(jià)ABZ、ABZ-HCl （25 mg·kg^-1）在大鼠體內(nèi)的藥動(dòng)學(xué)行為差異。結(jié)果 通過(guò)¹H-NMR證實(shí)了ABZ-HCl的形成；ABZ和ABZ-HCl的PXRD圖譜出現(xiàn)顯著差異；DVS實(shí)驗(yàn)結(jié)果表明，ABZ原藥的吸水性差，在90%相對(duì)濕度（RH）時(shí)吸水量?jī)H為3.86%，且吸附與解吸附曲線基本重合，而ABZ-HCl在開始的0~20% RH范圍內(nèi)迅速吸收水分，隨后質(zhì)量緩慢增加，在RH達(dá)到90%時(shí)吸水量為37.65%，在解吸過(guò)程中，ABZ-HCl的吸附曲線和解吸曲線不一致，存在滯后現(xiàn)象；TGA和DSC實(shí)驗(yàn)結(jié)果表明，2種物質(zhì)均無(wú)吸附水，ABZ-HCl較ABZ熔點(diǎn)降低；體外溶出實(shí)驗(yàn)結(jié)果顯示ABZ-HCl的表觀溶解度和IDR分別為ABZ的11.8、10.3倍；ABZ-HCl表現(xiàn)出良好的物理穩(wěn)定性。體內(nèi)藥動(dòng)學(xué)結(jié)果顯示，與ig ABZ原料相比，ABZ-HCl的AUC_{0~24 h}和C_max均顯著提高，分別提高了8.8和6.9倍。結(jié)論 所制備的ABZ-HCl可改善ABZ的溶解性能和口服生物利用度，且具有良好的物理穩(wěn)定性。

Objective Albendazole (ABZ) hydrochloric acid (HCl) salt (ABZ-HCl) was prepared, and the solid state properties, dissolution behavior in vitro, stability and oral bioavailability of the salt were evaluated. Method Crystallized ABZ-HCl was prepared by solvent evaporation method, and the prepared ABZ-HCl was validated by ¹H-NMR. Solid state properties were characterized by powder X-ray diffraction (PXRD), dynamic water adsorption (DVS), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). Measured the apparent solubility and intrinsic dissolution rate (IDR) of drug salts to observe their solubility and dissolution rate under different pH conditions. We conducted stability studies on ABZ-HCl under strong light irradiation (4500 ±500 lx), high humidity (92.5% ±5% RH), high temperature conditions (50 ±2)℃, and accelerated test conditions (40℃, 75% ±5% RH). Evaluated the pharmacokinetic behavior differences of ABZ and ABZ-HCl (25 mg·kg^-1) in rats.. Results The formation of ABZ-HCl was confirmed by ¹H-NMR. There was a significant difference in the PXRD spectra between ABZ and ABZ-HCl. The DVS experimental results showed that the water absorption of ABZ raw material was poor, with a water absorption rate of only 3.86% at 90% relative humidity (RH), and the adsorption and desorption curves basically overlapped. However, ABZ-HCl quickly absorbed water in the initial 0-20% RH range, and then slowly increased in mass. When RH reached 90%, the water absorption rate was 37.65%. During the desorption process, the adsorption and desorption curves of ABZ-HCl were inconsistent, and there was a lag phenomenon. The results of TGA and DSC experiments showed that both substances had no adsorbed water, and the melting point of ABZ-HCl was lower than that of ABZ. The results of in vitro dissolution experiments showed that the apparent solubility and IDR of ABZ-HCl were 11.8 and 10.3 times higher than those of ABZ, respectively. ABZ-HCl exhibited good physical stability. The in vivo pharmacokinetic results showed that compared with the ig ABZ raw material, the AUC_{0-24 h} and C_max of ABZ-HCl were significantly increased, by 8.8 and 6.9 times, respectively. Conclusion The prepared ABZ-HCl can improve the solubility and oral bioavailability of ABZ, and has good physical stability.

R943

青海省基礎(chǔ)研究計(jì)劃項(xiàng)目（2022-ZJ-748）