新型 Aceclofenac-l-胱氨酸和 Aceclofenac-脲共晶，具有增强的口服生物利用度。
Novel Aceclofenac-l-Cystine and Aceclofenac-Urea Cocrystals with Enhanced Oral Bioavailability.
机构信息
Goel Institute of Pharmacy and Sciences, Ayodhya Road, Lucknow, U.P., 226028, India.
Birla Institute of Technology, Ranchi, Jharkhand, 835 215, India.
出版信息
Curr Drug Deliv. 2021;18(8):1174-1181. doi: 10.2174/1567201818666210218103303.
AIM
Present research work focuses on the improvement of biopharmaceutical properties of aceclofenac (ACF) by the cocrystal approach.
BACKGROUND
ACF is one of the frequently used Nonsteroidal Anti-Inflammatory Drugs (NSAID). ACF is a BCS Class - II drug (low solubility and high permeability) with poor solubility and low oral bioavailability. Hence, the improvement in solubility and bioavailability of ACF is very crucial for successful product development. Nowadays, pharmaceutical cocrystals are considered a novel solid form of drugs. These cocrystals may have different physicochemical as well as biopharmaceutical properties as compared to the parent drug. In a previous study, the cocrystal of ACF (ACF-l-CYS NG and ACF-UREA NG) was successfully prepared and characterized. These cocrystals have shown superior solubility and dissolution rate than pure ACF in HCl buffer (pH 1.2). The synthesized cocrystals were also found non-hygroscopic and stable for 6 months under standard test settings. However, pharmacokinetic evaluation of these cocrystals has not been explored yet.
OBJECTIVE
The specific objective of this research work was the measurement of bioavailability and other pharmacokinetic parameters of ACF cocrystals prepared by the mechanochemical grinding method.
METHODS
Cocrystals of ACF with l-cystine and urea were prepared by neat grinding (NG) method and in-vivo oral bioavailability of prepared cocrystals was measured in Wistar rats. The plasma drug concentration was measured by high-performance liquid chromatography (HPLC), and the pharmacokinetic data was analyzed by "PK solver" software.
RESULTS
Percent relative bioavailability of ACF-l-CYS NG and ACF-UREA NG cocrystals in Wistar rats was found to be 242.05 ± 65.27and 178.93 ± 45.21 respectively, which were significantly higher (ANOVA, P < 0.05) than that of pure ACF.
CONCLUSION
The present study indicates that the enhanced aqueous solubility of the prepared cocrystals leads to enhanced oral bioavailability of ACF. Thus, the cocrystals may be an alternative crystalline form of the drug that can enhance the solubility, dissolution rate, and oral bioavailability of many poorly soluble drugs.
目的
本研究工作旨在通过共晶方法改善醋氯芬酸（ACF）的生物制药特性。
背景
ACF 是常用的非甾体抗炎药（NSAID）之一。ACF 是 BCS 分类 II 类药物（低溶解度和高通透性），溶解度低，口服生物利用度低。因此，提高 ACF 的溶解度和生物利用度对于成功开发产品非常重要。如今，药物共晶被认为是药物的一种新型固体形式。与母体药物相比，这些共晶可能具有不同的物理化学和生物制药特性。在之前的研究中，成功制备和表征了 ACF 的共晶（ACF-l-CYS NG 和 ACF-UREA NG）。与纯 ACF 相比，这些共晶在 HCl 缓冲液（pH 1.2）中表现出更高的溶解度和溶解速率。在标准测试条件下，合成的共晶也被发现不易吸湿且稳定 6 个月。然而，这些共晶的药代动力学评估尚未得到探索。
目的
本研究工作的具体目的是测量通过机械化学研磨法制备的 ACF 共晶的生物利用度和其他药代动力学参数。
方法
通过 neat grinding（NG）方法制备 ACF 与 l-胱氨酸和尿素的共晶，并在 Wistar 大鼠中测量制备共晶的口服生物利用度。通过高效液相色谱法（HPLC）测量血浆药物浓度，并通过“PK solver”软件分析药代动力学数据。
结果
在 Wistar 大鼠中，ACF-l-CYS NG 和 ACF-UREA NG 共晶的相对生物利用度分别为 242.05%±65.27%和 178.93%±45.21%，明显高于纯 ACF（ANOVA，P<0.05）。
结论
本研究表明，所制备共晶的水溶解度增加导致 ACF 的口服生物利用度增加。因此，共晶可能是一种替代药物的晶体形式，可以提高许多难溶性药物的溶解度、溶解速率和口服生物利用度。
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