Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Japan.
Department of Pharmaceutical Physical Chemistry, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo, Matsuyama, Ehime, Japan.
J Pharm Sci. 2018 Jan;107(1):446-452. doi: 10.1016/j.xphs.2017.05.023. Epub 2017 May 24.
Meloxicam (MEL) shows a slow onset of action in severe pain patients on account of delayed gastric motility. This study aimed to develop an amorphous solid dispersion (ASD) of MEL to achieve rapid oral absorption in severe pain patients. ASD formulations of MEL with hydroxypropylmethylcellulose (ASD-MEL/HPMC) and polyacrylates and polymethacrylates (ASD-MEL/EUD) were prepared and physicochemically characterized. Oral absorption behavior of MEL samples was also clarified in both normal and propantheline (PPT)-pretreated rats with impaired gastric motility. MEL in the formulations was amorphous, and ASD formulations of MEL exhibited high dissolution behavior in acidic solution. After oral administration of crystalline MEL (1 mg-MEL/kg), a 69% reduction in AUC was observed between normal and PPT-pretreated rats. For orally dosed ASD-MEL/HPMC (1 mg-MEL/kg), there were approximately 9- and 12-fold increases of AUC in normal and PPT-pretreated rats, respectively, in comparison with crystalline MEL (1 mg-MEL/kg). However, the oral absorption behavior of ASD-MEL/EUD (1 mg-MEL/kg) was low and similar to that of crystalline MEL. The infrared spectroscopic study revealed potent interactions between MEL and EUD, possibly leading to marked attenuation of MEL absorption. This ASD approach might provide rapid oral absorption of MEL in severe pain patients, possibly leading to better clinical outcomes.
美洛昔康（MEL）在严重疼痛患者中由于胃动力延迟而表现出起效缓慢。本研究旨在开发 MEL 的无定形固体分散体（ASD），以实现严重疼痛患者的快速口服吸收。制备了 MEL 与羟丙甲纤维素（ASD-MEL/HPMC）和聚丙烯酸酯和聚甲基丙烯酸酯（ASD-MEL/EUD）的 ASD 制剂，并对其理化性质进行了表征。还在胃动力受损的正常和丙戊茶碱（PPT）预处理大鼠中阐明了 MEL 样品的口服吸收行为。制剂中的 MEL 为无定形，ASD 制剂的 MEL 在酸性溶液中表现出高溶解行为。经口给予结晶 MEL（1 mg-MEL/kg）后，正常和 PPT 预处理大鼠的 AUC 减少了 69%。与结晶 MEL（1 mg-MEL/kg）相比，口服给予 ASD-MEL/HPMC（1 mg-MEL/kg）时，正常和 PPT 预处理大鼠的 AUC 分别增加了约 9 倍和 12 倍。然而，ASD-MEL/EUD（1 mg-MEL/kg）的口服吸收行为较低，与结晶 MEL 相似。红外光谱研究表明 MEL 与 EUD 之间存在强烈相互作用，可能导致 MEL 吸收明显减弱。这种 ASD 方法可能为严重疼痛患者提供 MEL 的快速口服吸收，从而可能带来更好的临床结果。
Zotero 插件