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一种新的酮洛芬钠结晶盐:固态特性、溶解度和稳定性。

A New Crystalline Ketoprofen Sodium Salt: Solid-State Characterization, Solubility, and Stability.

机构信息

Faculty of Pharmaceutical Sciences, Federal University of Alfenas (UNIFAL-MG), Alfenas, Minas Gerais 37130-001, Brazil.

Institute of Chemistry, Federal University of Alfenas (UNIFAL-MG), Alfenas, Minas Gerais 37130-001, Brazil.

出版信息

J Pharm Sci. 2022 Jun;111(6):1674-1681. doi: 10.1016/j.xphs.2021.11.011. Epub 2021 Nov 20.


DOI:10.1016/j.xphs.2021.11.011
PMID:34808219
Abstract

Ketoprofen (KTP) is an Active Pharmaceutical Ingredient (API) that has low solubility in aqueous solvents. The use of KTP salts has attracted attention due to its improvements in terms of solubility, tolerability, higher rate and extent of absorption, and faster onset of the therapeutic effect. In this work, a crystalline KTP sodium salt (coded as KTP-Na) was successfully obtained and widely characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), solubility and accelerated stability studies. XRD results showed that KTP-Na is not yet reported in the literature. Moreover, FTIR, DSC and TGA were useful for differentiation of KTP-Na from the KTP commercialized form (coded as KTP-R1). The solubility of KTP-Na in water was about 80 times greater than the KTP-R1. However, KTP-Na showed lower physical stability in storage conditions at 40 ± 2°C/ 75% ± 5% RH when compared to KTP-R1, which was shown to be related to a high hygroscopicity of KTP-Na. Therefore, due to its higher solubility, KTP-Na may be a viable alternative for use in solid dosage forms. However, the presence of moisture must be strictly controlled to avoid water absorption and consequent amorphization.

摘要

酮洛芬(KTP)是一种活性药物成分(API),在水性溶剂中的溶解度较低。由于其在溶解度、耐受性、更高的吸收率和吸收速度、更快的治疗效果方面的改善,KTP 盐的使用引起了关注。在这项工作中,成功获得了结晶 KTP 钠盐(编码为 KTP-Na),并通过 X 射线粉末衍射(XRD)、傅里叶变换红外光谱(FTIR)、差示扫描量热法(DSC)、热重分析(TGA)、溶解度和加速稳定性研究对其进行了广泛表征。XRD 结果表明,KTP-Na 在文献中尚未报道。此外,FTIR、DSC 和 TGA 有助于将 KTP-Na 与商业化的 KTP 形式(编码为 KTP-R1)区分开来。KTP-Na 在水中的溶解度约为 KTP-R1 的 80 倍。然而,与 KTP-R1 相比,KTP-Na 在 40°C/75%±5%RH 的储存条件下表现出较低的物理稳定性,这与 KTP-Na 的高吸湿性有关。因此,由于其较高的溶解度,KTP-Na 可能是用于固体制剂的一种可行替代品。然而,必须严格控制水分的存在,以避免吸水和随后的非晶化。

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[1]
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[3]
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[4]
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