Department of Pharmaceutics, College of Pharmacy, King Saud University , Riyadh , Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University , Alkharj , Saudi Arabia.
Drug Dev Ind Pharm. 2019 Oct;45(10):1610-1616. doi: 10.1080/03639045.2019.1645161. Epub 2019 Jul 29.
Mefenamic acid (MA) has been reported as a weakly soluble drug which presents weak absorption upon oral administration using conventional formulations. Solid dispersions (SDs) have been investigated extensively in literature for enhancing the solubility and bioavailability of weakly-soluble molecules. Hence, the aim of proposed study was to prepare MA novel formulations in the form of SDs using hot-melt extrusion technology in order to enhance its palatability, bioavailability, and pharmacodynamics effects/anti-inflammatory efficacy. Various SDs of MA were prepared using hot-melt extrusion technology, characterized physically and investigated for dissolution tests. Optimized SD formulations of MA were being subjected to palatability, pharmacodynamics, and pharmacokinetic studies in rats. Optimized SD of MA showed significant rat palatability tastes as compared with pure and marketed MA ( < .05). Anti-inflammatory efficacy of 20% SD and 25% SD of MA was found to be 86.44 and 89.83%, respectively, in comparison with 74.57 and 78.24% by pure MA and marketed MA, respectively. The anti-inflammatory efficacy of optimized SD was found to be significant as compared with pure and marketed MA ( < .05). The oral absorption of MA from optimized 20% SD was also noted as statistically significant as compared with pure MA ( < .05). The relative bioavailability of MA from 20 and 25% SDs was 2.97 and 2.24-folds higher than pure MA. The results of this study suggested that SDs prepared using hot-melt extrusion technology are capable to enhance palatability, anti-inflammatory efficacy, and oral bioavailability of MA in comparison with pure drug.
甲芬那酸(MA)已被报道为一种低溶解度药物,常规制剂口服后吸收性较弱。固体分散体(SDs)在文献中已被广泛研究,以提高低溶解度分子的溶解度和生物利用度。因此,本研究旨在通过热熔挤出技术制备 MA 的新型 SD 制剂,以提高其口感、生物利用度和药效/抗炎效果。采用热熔挤出技术制备了各种 MA 的 SD,并对其进行了物理性质表征和溶解试验研究。MA 的优化 SD 制剂正在大鼠中进行适口性、药效学和药代动力学研究。与纯 MA 和市售 MA( < .05)相比,MA 的优化 SD 表现出显著的大鼠口感。MA 的 20%SD 和 25%SD 的抗炎效果分别为 86.44%和 89.83%,而纯 MA 和市售 MA 的抗炎效果分别为 74.57%和 78.24%。与纯 MA 和市售 MA 相比,优化 SD 的抗炎效果具有统计学意义( < .05)。从优化的 20%SD 中口服吸收 MA 的效果也被认为与纯 MA 相比具有统计学意义( < .05)。20%和 25%SD 中 MA 的相对生物利用度分别比纯 MA 高 2.97 倍和 2.24 倍。本研究结果表明,与纯药物相比,热熔挤出技术制备的 SD 能够提高 MA 的口感、抗炎效果和口服生物利用度。