Inclusion Complexes of α and β-cyclodextrin with Canagliflozin Hemihydrate: Design and Characterization.

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY

Current pharmaceutical design Pub Date : 2025-08-15 DOI:10.2174/0113816128384484250729091344

Priyanka Gauniya, Chitra, Mukesh Pandey, Radheshyam, Ajay Semalty, Mukul Gupta, Archna Sagdeo, Mona Semalty

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引用次数: 0

Abstract

Introduction: Canagliflozin hemihydrate (CANA), an antidiabetic drug that functions as a sodiumglucose co-transporter 2 (SGLT2) inhibitor, is classified under the Biopharmaceutical Classification System (BCS) as a Class IV drug, characterized by low solubility and low permeability. This study aimed to enhance the solubility, dissolution, and permeability of CANA by preparing its inclusion complexes with α- cyclodextrin (α-CD) and β-cyclodextrin (β-CD), followed by characterization of their crystalline and biopharmaceutical properties.

Methods: The solubility of CANA in aqueous medium and phase solubility with α and β-cyclodextrin were conducted. The inclusion complexes in different CANA: α-CD ratios (1:0.25 to 1:6 mM) and CANA: β-CD ratios (1:0.50 to 1:8 mM) were prepared using the freeze-drying method. The complexes were subjected to drug content analysis, Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRPD), angle- dispersive X-ray diffraction (ADXRD), in vitro dissolution, and permeation studies.

Results: Phase solubility study indicated significant improvements in aqueous solubility of CANA with α-CD and β-CD. The solubility of CANA increased significantly (more than 100-fold in BCD8 with 0.577 mg/mL) upon complexation. BCD8 (1:7) with 97.366% and ACD6 (1:4) with 94.6% showed the highest % drug content. FTIR confirmed interactions between CANA and CDs due to the disappearance or shifting of some characteristic peaks (e.g., 3390.68 to 3268.91 cm-1 and 1078.07 to 1024.06 cm-1 in ACD6, while 3265.05 to 3268.91 cm⁻¹ and 1025.99 to 1024.06 cm⁻¹ in ACD7).

Discussion: XRPD and ADXRD showed the crystalline nature of CANA and CDs, while the complexes exhibited amorphization with diffused peaks. The lowest crystallite size was observed in ACD6 (449.688) and the highest in ACD3 (966.936 Å). D-spacing was found to be smallest in ACD8 (0.722 Å) and BCD6 (4.080 Å), and the highest in ACD1 (7.276 Å), BCD7, and BCD8 (7.063 Å). The drug release ranged from 64.265% (ACD3) to 94.306% (BCD7) and increased with lower crystallinity. ACD8 (87.33%) and BCD7 (93.41%) exhibited the highest % of drug permeability.

Conclusion: Inclusion complexation with α-CD and β-CD significantly improved the solubility and dissolution of CANA in aqueous medium. These findings suggest that cyclodextrin-based inclusion complexes offer a promising approach to enhancing the biopharmaceutical performance of poorly soluble drugs, such as CANA.

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半水合卡格列净与α、β-环糊精包合物的设计与表征。

简介：半水合Canagliflozin （Canagliflozin hemihydrate， CANA）是一种具有钠-葡萄糖共转运蛋白2 （SGLT2）抑制剂功能的降糖药物，在生物制药分类系统（BCS）中被列为IV类药物，具有低溶解度和低通透性的特点。本研究旨在通过制备α-环糊精（α- cd）和β-环糊精（β-CD）包合物来提高CANA的溶解度、溶解性和渗透性，并对其晶体性质和生物制药性质进行表征。方法：测定CANA在水介质中的溶解度以及与α和β-环糊精的相溶解度。采用冷冻干燥法制备不同CANA: α-CD比（1:0.25 ~ 1:6 mM）和CANA: β-CD比（1:0.50 ~ 1:8 mM）的包合物。对配合物进行了药物含量分析、傅里叶变换红外光谱（FTIR）、x射线粉末衍射（XRPD）、角色散x射线衍射（ADXRD）、体外溶出度和渗透研究。结果：相溶解度研究表明，α-CD和β-CD对CANA的水溶性有显著改善。与BCD8 （0.577 mg/mL）络合后，CANA的溶解度显著增加（超过100倍）。BCD8（1:7）占97.366%,ACD6（1:4）占94.6%。FTIR证实了CANA和cd之间的相互作用，因为一些特征峰的消失或转移（例如，ACD6中的3390.68至3268.91 cm-1和1078.07至1024.06 cm-1，而ACD7中的3265.05至3268.91 cm-1和1025.99至1024.06 cm-1）。讨论：XRPD和ADXRD显示了CANA和CDs的结晶性质，而配合物表现出非晶化和扩散峰。ACD6的晶粒尺寸最小（449.688），ACD3的晶粒尺寸最大（966.936 Å）。d -间距在ACD8 （0.722 Å）和BCD6 （4.080 Å）中最小，在ACD1 （7.276 Å）、BCD7和BCD8 （7.063 Å）中最大。药物释放范围为64.265% (ACD3) ~ 94.306% (BCD7)，随结晶度的降低而增加。ACD8（87.33%）和BCD7（93.41%）的药物通透率最高。结论：α-CD和β-CD包合可显著提高CANA在水介质中的溶解度和溶出度。这些发现表明，基于环糊精的包合物为提高难溶性药物（如CANA）的生物制药性能提供了一种有希望的方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current pharmaceutical design 医学-药学

CiteScore

6.30

自引率

0.00%

发文量

302

审稿时长

2 months

期刊介绍： Current Pharmaceutical Design publishes timely in-depth reviews and research articles from leading pharmaceutical researchers in the field, covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area guest edited by an acknowledged authority in the field. Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design including: medicinal chemistry, pharmacology, drug targets and disease mechanism.