新型 Aceclofenac 与 l-胱氨酸共晶：虚拟共晶筛选、机械化学合成及理化性质研究。

Novel Aceclofenac Cocrystals with l-Cystine: Virtual Coformer Screening, Mechanochemical Synthesis, and Physicochemical Investigations.

机构信息

Department of Pharmaceutical Chemistry, Goel Institute of Pharmacy and Sciences, Faizabad Road, Lucknow, U.P., 226028, India.

Department of Pharmaceutical Chemistry, Birla Institute of Technology, Ranchi, Jharkhand, 835 215, India.

出版信息

Curr Drug Deliv. 2021;18(1):88-100. doi: 10.2174/1567201817666200817110949.

DOI:10.2174/1567201817666200817110949

PMID:32807053

Abstract

AIM

Current work focuses on the improvement of the solubility and dissolution of ACF by the cocrystal approach.

BACKGROUND

Aceclofenac (ACF) is one of the commonly used Nonsteroidal Anti-Inflammatory Drug (NSAID) representing a variety of therapeutic applications including management of pain, inflammation, rheumatoid arthritis, and osteoarthritis, . But very low solubility and dissolution rate of ACF compromise its therapeutic utility. Now a day's cocrystallization technique has emerged as a novel technique for modulation of the said problems.

OBJECTIVE

The Specific objectives of this research work were mechanochemical synthesis, characterization, and performance evaluation of aceclofenac cocrystal.

METHODS

ACF was screened with various pharmaceutically acceptable coformers (Selected from GRAS and EAFUS list) using MOPAC software and physical screening method to find out novel cocrystals of ACF with enhanced solubility and dissolution rate. Novel cocrystals (multi-component crystalline solid) of ACF with l-cystine were prepared by a neat grinding method and by liquid assisted grinding method. The synthesized cocrystals (ACF-l-CYS NG and ACF-l-CYS LAG) were characterized carefully by Differential Scanning Calorimetry (DSC), Infrared Spectroscopy (IR), and Powder XRay Diffraction (PXRD) to verify the formation of the cocrystals. Pharmaceutically significant properties such as powder dissolution rate, solubility, and stability of the prepared cocrystals were evaluated.

RESULTS

Compared to pure ACF, the prepared cocrystals showed superior solubility and dissolution rate. The prepared cocrystals were found to be stable and non-hygroscopic under study conditions.

CONCLUSION

The cocrystallization technique was successfully utilized to increase the solubility and dissolution rate of aceclofenac.

摘要

目的

目前的工作重点是通过共晶方法提高 ACF 的溶解度和溶解率。

背景

醋氯芬酸（ACF）是常用的非甾体抗炎药（NSAID）之一，具有多种治疗用途，包括疼痛、炎症、类风湿关节炎和骨关节炎的治疗。但是，ACF 的溶解度和溶解速率非常低，这影响了其治疗效果。如今，共晶技术已成为一种用于调节这些问题的新技术。

目的

本研究工作的具体目标是机械化学合成、表征和评估醋氯芬酸共晶。

方法

使用 MOPAC 软件和物理筛选方法，筛选出各种可接受的药用共晶形成剂（选自 GRAS 和 EAFUS 清单），以发现具有增强溶解度和溶解速率的 ACF 新型共晶。通过干法研磨和液辅助研磨法制备 ACF 与 l-胱氨酸的新型共晶（多组分结晶固体）。通过差示扫描量热法（DSC）、红外光谱（IR）和粉末 X 射线衍射（PXRD）仔细表征合成的共晶（ACF-l-CYS NG 和 ACF-l-CYS LAG），以验证共晶的形成。评估了所制备共晶的药用重要性质，如粉末溶解速率、溶解度和稳定性。