Novel crystalline solid dispersion of tranilast with high photostability and improved oral bioavailability
Novel crystalline solid dispersion of tranilast with high photostability and improved oral bioavailability
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DOI：
10.1016/j.ejps.2009.12.009
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发表时间：
2010-02-19
影响因子：
4.6
通讯作者：
Yamada, Shizuo
中科院分区：
文献类型：
--
作者：
Kawabata, Yohei;Yamamoto, Kiyoshi;Yamada, Shizuo
曲尼司特（TL）是一种抗过敏药，临床上广泛用于治疗支气管哮喘、特应性鼻炎、特应性皮炎和瘢痕疙瘩。然而，TL的治疗潜力可能会受到部分限制，因为它的溶解性，生物利用度和光稳定性差。为了克服这些缺点，采用湿磨技术制备TL结晶固体分散体（CSD/TL），目的是改善理化和药动学性质。通过激光衍射和动态光散射进行粒度分析，扫描电子显微镜进行形态分析，粉末X-射线衍射和差示扫描量热法进行结晶度评估，其特征在于制备的制剂的物理化学性质。CSD/TL中的TL颗粒似乎是直径为122 nm的结晶，并且CSD/TL与结晶TL相比在溶解行为上表现出显著的改善。在UVA/B（250 W/m（2））的照射下，TL的溶液和无定形固体分散体具有很高的光降解性，而CSD/TL具有很高的光化学稳定性。口服CSD/TL后。与结晶TL相比，观察到TL暴露增强，C-max和AUC分别增加60倍和32倍。根据这些观察，结合溶出和药代动力学行为，结晶固体分散策略将有效地提高TL的生物利用度，具有高的光化学稳定性。(C)2009爱思唯尔有限公司版权所有。
Tranilast (TL) is an anti-allergic agent and widely used in the clinical treatment of bronchial asthma, atopic rhinitis, atopic dermatitis and keloids. However, therapeutic potential of TL could be partly limited because of its poor solubility, bioavailability, and photostability. To overcome these drawbacks, crystalline solid dispersion of TL (CSD/TL) was prepared by wet-milling technique with aim of improving physicochemical and pharmacokinetic properties. Physicochemical properties of the formulations prepared were characterized by laser diffraction and dynamic light scattering for particle size analysis, scanning electron microscope for morphological analysis, and powder X-ray diffraction and differential scanning calorimetry for crystallinity assessment. TL particles in CSD/TL appeared to be crystalline with diameter of 122 nm, and CSD/TL exhibited marked improvement in the dissolution behavior as compared to crystalline TL. Under irradiation of UVA/B (250W/m(2)), solution and amorphous solid dispersion of TL were found to be highly photodegradable, whereas high photochemical stability was seen in CSD/TL. After oral administration of CSD/TL. enhanced TL exposure was observed with increase of C-max and AUC by 60- and 32-fold, respectively, as compared to crystalline TL. According to these observations, taken together with dissolution and pharmacokinetic behaviors, crystalline solid dispersion strategy would be efficacious to enhance bioavailability of TL with high photochemical stability. (C) 2009 Elsevier B.V. All rights reserved.