热熔挤压Aceclofenac-Soluplus®固体分散体:增强溶解的混溶性和药物载体相互作用的机制观点。

IF 3.4 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Likhitha U, Roushan Bharti, Reema Narayan, Chetan H Mehta, Usha Yogendra Nayak
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引用次数: 0

摘要

Aceclofenac (ACF)是一种非甾体抗炎药(NSAID),与Soluplus®(SOLP)配制,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,即利用热熔挤压(HME)制备Aceclofenac-Soluplus®固体分散体(ACF-SOLP),与之前研究的纳米乳液技术形成对比。HME技术促进了聚合物基质内均匀的药物分布,提高了ACF的溶解速度。以1:8 (HM4)评价ACF与SOLP的不同重量比,确定其为最优选择。ACF以无定形分散在SOLP中,与纯ACF及其物理混合物相比,HM4的药物释放明显增加。体内药动学数据显示,HM4显著改善Cmax(7.1±0.14µg/ml)和AUC(12.1±1.30µg-h/ml)。此外,分子动力学模拟表明,聚合物广泛分布在ACF- solp的超分子结构中,ACF位于中心位置,证实了组分之间的良好相互作用。利用SOLP的亲水性,固体分散体增强了ACF的溶解,而HME则协同增强了ACF的溶解。这种方法提出了一种令人信服的替代传统方法,为配制难溶性药物提供了新的可能性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hot Melt Extruded Aceclofenac-Soluplus® Solid Dispersion: Mechanistic View of Miscibility and Drug-Carrier Interactions for Enhanced Dissolution.

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 Cmax (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.

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来源期刊
AAPS PharmSciTech
AAPS PharmSciTech 医学-药学
CiteScore
6.80
自引率
3.00%
发文量
264
审稿时长
2.4 months
期刊介绍: AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.
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