Purpose

Aceclofenac is a nonsteroidal anti-inflammatory drug (NSAID) belonging to BCS Class II, has a constraint over its therapeutic benefits owing to its poor aqueous solubility.

Methods

In this study, co-amorphous mixtures of Aceclofenac (ACE) with Aspartame (ASPA) of various molar ratios at specific milling times were produced through ball milling (BM) technique. The characterization was done using FTIR, DSC and PXRD. The pellets formulation was prepared by extrusion spheronization method using 3² full factorial design. The optimized formulation was evaluated for in-vitro and in-vivo performance.

Results

Amongst the co amorphous mixtures and pure ACE studied for solubility, ACE: ASPA (1:1) showed the significant increase in solubility and was further formulated as pellets. Solid-state characterization of mixture revealed amorphization of ACE after 120 min of ball milling. In-vitro dissolution study data of F4 pellets formulation revealed (99.00 ± 3.59%) significant increase (P < 0.005) compared to pure drug (50.12 ± 2.52%) and other formulations. The in-vivo studies reveal a significant increase in percent inhibition of inflammation (61.7%) of the prepared formulation (p < 0.05) as compared to the marketed formulation (53.19%), and pure drug (46.8%).

Conclusion

Therefore, the prepared pellets of co-amorphous mixture of aceclofenac and aspartame, boost the solubility and stability of aceclofenac which has a potential to be a promising approach in the management of pain.

Graphical Abstract

中文翻译：

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含有醋氯芬酸 Co 无定形混合物的速释微丸制剂的设计和开发：体外和体内研究

目的

醋氯芬酸是一种属于 BCS II 类的非甾体抗炎药 (NSAID)，由于其水溶性差，其治疗效果受到限制。

方法

在这项研究中，通过球磨（BM）技术生产了不同摩尔比的醋氯芬酸（ACE）与阿斯巴甜（ASPA）在特定研磨时间下的共无定形混合物。使用 FTIR、DSC 和 PXRD 进行表征。采用3× ²全因子设计通过挤出滚圆法制备微丸制剂。对优化配方的体外和体内性能进行了评估。

结果

在共无定形混合物和纯 ACE 溶解度研究中，ACE: ASPA (1:1) 显示溶解度显着增加，并进一步配制成颗粒。混合物的固态表征显示 ACE 在球磨 120 分钟后发生非晶化。F4 微丸制剂的体外溶出研究数据显示，与纯药 (50.12 ± 2.52%) 和其他制剂相比，F4 微丸制剂的体外溶出度显着增加 (99.00 ± 3.59%) (P < 0.005)。体内研究表明，与市售制剂 (53.19%) 和纯药物 (46.8%) 相比，制备的制剂 (p < 0.05) 的炎症抑制百分比 (61.7%) 显着增加。

结论

因此，制备的醋氯芬酸和阿斯巴甜的共无定形混合物颗粒提高了醋氯芬酸的溶解度和稳定性，这有可能成为治疗疼痛的有前途的方法。

图形概要