U Likhitha, Bharti Roushan, Narayan Reema, Mehta Chetan H, Nayak Usha Yogendra
Center for Drug Delivery Technologies, Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
AAPS PharmSciTech. 2025 Jul 1;26(6):180. doi: 10.1208/s12249-025-03173-w.
Aceclofenac (ACF), a Non-Steroidal Anti-Inflammatory Drug (NSAID), is formulated with Soluplus® (SOLP) to enhance solubility and bioavailability. This study presents a distinct approach by utilizing Hot Melt Extrusion (HME) to prepare Aceclofenac-Soluplus® solid dispersion (ACF-SOLP), in contrast to the previously investigated nanoemulsion technique. The HME technique facilitates a uniform drug distribution within the polymer matrix, increasing ACF's dissolution rate. Different weight ratios of ACF and SOLP were assessed with 1:8 (HM4), which proved to be the optimal choice. ACF is dispersed within SOLP in its amorphous state, and HM4 exhibited a significant increase in drug release as compared to pure ACF and its physical mixture. In vivo pharmacokinetic data of HM4 demonstrated a drastic improvement in the C (7.1 ± 0.14 µg/ml) and AUC (12.1 ± 1.30 µg-h/ml). Further, molecular dynamics simulation revealed that the polymer is widely dispersed within the supramolecular architecture of ACF-SOLP, with ACF positioned centrally, confirming the favorable interactions between the components. Leveraging the hydrophilic nature of the SOLP, the solid dispersion demonstrated enhanced dissolution of ACF, while HME synergistically reinforced the combination. This approach presents a compelling alternative to traditional methods, unlocking new possibilities for formulating poorly soluble drugs.
醋氯芬酸（ACF）是一种非甾体抗炎药（NSAID），与Solupuls®（SOLP）一起制成制剂以提高溶解度和生物利用度。本研究提出了一种独特的方法，即利用热熔挤出（HME）技术制备醋氯芬酸 - Solupuls®固体分散体（ACF - SOLP），这与之前研究的纳米乳液技术不同。HME技术有助于药物在聚合物基质中均匀分布，提高ACF的溶解速率。评估了ACF和SOLP的不同重量比，其中1:8（HM4）被证明是最佳选择。ACF以无定形状态分散在SOLP中，与纯ACF及其物理混合物相比，HM4的药物释放显著增加。HM4的体内药代动力学数据表明，其C（7.1±0.14μg/ml）和AUC（12.1±1.30μg - h/ml）有显著改善。此外，分子动力学模拟表明，聚合物广泛分散在ACF - SOLP的超分子结构中，ACF位于中心位置，证实了各组分之间的良好相互作用。利用SOLP的亲水性，固体分散体显示出ACF的溶解增强，而HME协同增强了这种组合。这种方法为传统方法提供了一种有吸引力的替代方案，为难溶性药物的制剂开发开辟了新的可能性。
