Chitosan-telmisartan polymeric cocrystals for improving oral absorption: In vitro and in vivo evaluation
Chitosan-telmisartan polymeric cocrystals for improving oral absorption: In vitro and in vivo evaluation
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DOI：
10.1016/j.ijbiomac.2019.03.141
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发表时间：
2019-06-15
影响因子：
8.2
通讯作者：
Jang, Hyun Tae
中科院分区：
文献类型：
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作者：
Ganesh, Mani;Ubaidulla, Udhumansha;Jang, Hyun Tae
本研究描述了壳聚糖-替米沙坦（TEL）聚合物共晶的开发，以提高口服生物利用度的TEL，这是一个口服溶解度和生物利用度差。以生物高分子壳聚糖为原料，柠檬酸钠为盐析剂制备了壳聚糖高分子共晶。通过红外光谱、扫描电镜、差示扫描量热仪（DSC）、热重分析（TGA）和X射线粉末衍射（PXRD）对共晶进行了表征。在用磷酸盐缓冲液（pH 7.4）进行的溶解度研究中，与纯药物相比，用共晶观察到TEL的溶解度改善。以大鼠为动物模型，研究了共晶单剂量口服给药后的体内药代动力学特性。结果表明，与0.96 μ g/ml的纯TEL相比，共晶体的血浆药物浓度（C-max）增加了1.47 μ g/ml，生物利用度（F%）增加了一倍，即，共晶体通过紧密连接调节增加了药物的溶解度和细胞旁药物吸收。此外，当与纯药物的0.0048 h（-1）相比时，消除常数K-el产生约0.0085 h（-1）的更高值，沿着具有改善的AUC（14.62 μ g/ml）。(C)2019爱思唯尔B. V.保留所有权利。
This study describes the development of polymeric cocrystals of chitosan-telmisartan (TEL) to improve the oral bioavailability of TEL, which has poor oral solubility and bioavailability. The polymeric cocrystal was prepared using chitosan a biopolymer with the aid of sodium citrate as a salting-out agent. The cocrystals were characterized by FT-IR spectroscopy, scanning electron microscopy, differential scanning calorimeteri (DSC), thermogravimetric analysis (TGA), and powder X-ray diffraction (PXRD). The improved solubility of TEL was observed with cocrystals as compared to that of pure drug in solubility studies with phosphate buffer (pH 7.4). The in vivo pharmacokinetics properties of cocrystal were studied by an animal model using rats after a single dose oral administration. The results showed an increased plasma drug concentration (C-max) of 1.47, mu g/ml for cocrystals when compared to pure TEL with 0.96 mu g/ml with one-fold increased bioavailability (F%) that is, the cocrystals increases the solubility of the drug and the paracellular drug absorption by tight junction modulation. Further the elimination constant K-el resulted with higher value of about 0.0085 h(-1) when compared to pure drug with0.0048h(-1) along with improved AUC (14.62 mu g/ml). (C) 2019 Elsevier B.V. All rights reserved.