Complexation of telmisartan with cyclodextrins as a tool of solubility enhancement: A comparative analysis of influence of the cyclodextrin type and method of solid dispersion preparation

IF 4.9 2区化学 Q2 CHEMISTRY, PHYSICAL

Colloids and Surfaces A: Physicochemical and Engineering Aspects Pub Date : 2024-10-29 DOI:10.1016/j.colsurfa.2024.135662

Angelica Sharapova, Marina Ol’khovich, Svetlana Blokhina

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引用次数: 0

Abstract

Cardiovascular telmisartan (TMS) was complexed with modified cyclodextrins (CD) aiming at improvement of its poor solubility which results into low bioavailability. Inclusion complexes with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD) in liquid and solid state was evaluated for first time. Phase solubility isotherm diagrams of TMS versus the CD concentration were plotted in a buffer pH 7.4. It was found that TMS/CD complexes are formed in solution in an equimolar stoichiometric ratio of 1:1. The aqueous solubility of TMS with the addition of 0.05 mol·L⁻¹ HP-β-CD increased by 23 times and was 38.9·10⁻⁵ mol·L⁻¹, and the presence of the same amount of SBE-β-CD in solution increased the solubility of the drug by 7 times, reaching a value of 12.6·10⁻⁵ mol·L⁻¹.The binding constants were found to 468 and 114 L·mol⁻¹ for HP-β-CD and SBE-β-CD, respectively. Novel solid forms of TMS with both CDs were prepared using the grinding and evaporation approaches. Successful formation of supramolecular TMS/HP-β-CD and TMS/SBE-β-CD solid complexes was confirmed by FTIR, PXRD, DSC, TGA and SEM. The residual crystallinity of all obtained solid dispersions of TMS/CD did not exceed 10 %. Supersaturation was observed during the dissolution of all the solid complexes. The grinding technique was found to be more advantageous as it ensured the biggest improvement of the drug maximum concentration in the aqueous solution: the TMS solubility in the TMS/HP-β-CD(gr) and TMS/SBE-β-CD(gr) solid complexes increased by 27 and 33 times, respectively. Besides, polyvinyl pyrrolidone (PVP) and polyethylene glycol (PEG) were tested as crystallization inhibitors. Addition of 1 wt% PVP as a stabilizer is a promising approach for the preparation of TMS pharmaceutical formulations with improved bioavailability.

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替米沙坦与环糊精的络合作为一种提高溶解度的工具：环糊精类型和固体分散体制备方法影响的比较分析

心血管药物替米沙坦（TMS）与改性环糊精（CD）络合，旨在改善其溶解性差导致生物利用率低的问题。首次评估了与 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) 和 sulfobutylether-β-cyclodextrin (SBE-β-CD) 在液态和固态下的包合物。在 pH 值为 7.4 的缓冲液中绘制了 TMS 与 CD 浓度的相溶解等温线图。结果发现，TMS/CD 复合物在溶液中的等摩尔化学计量比为 1:1。加入 0.05 mol-L-1 HP-β-CD 后，TMS 的水溶性增加了 23 倍，达到 38.9-10-5 mol-L-1，而溶液中存在等量的 SBE-β-CD 时，药物的溶解度增加了 7 倍，达到 12.6-10-5 mol-L-1。利用研磨和蒸发方法制备了含有这两种 CD 的新型 TMS 固体。傅立叶变换红外光谱（FTIR）、聚X射线衍射（PXRD）、数显分析（DSC）、热重分析（TGA）和扫描电子显微镜（SEM）证实了超分子 TMS/HP-β-CD 和 TMS/SBE-β-CD 固体复合物的成功形成。所有获得的 TMS/CD 固体分散体的残余结晶度均不超过 10%。在所有固体复合物的溶解过程中都观察到了过饱和现象。研究发现研磨技术更具优势，因为它能最大程度地提高水溶液中的药物最大浓度：TMS/HP-β-CD(gr) 和 TMS/SBE-β-CD(gr) 固体复合物中的 TMS 溶解度分别提高了 27 倍和 33 倍。此外，还测试了聚乙烯吡咯烷酮（PVP）和聚乙二醇（PEG）作为结晶抑制剂。添加 1 wt% 的 PVP 作为稳定剂是制备生物利用度更高的 TMS 药物制剂的一种可行方法。

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来源期刊

Colloids and Surfaces A: Physicochemical and Engineering Aspects 化学-物理化学

CiteScore

8.70

自引率

9.60%

发文量

2421

审稿时长

56 days

期刊介绍： Colloids and Surfaces A: Physicochemical and Engineering Aspects is an international journal devoted to the science underlying applications of colloids and interfacial phenomena. The journal aims at publishing high quality research papers featuring new materials or new insights into the role of colloid and interface science in (for example) food, energy, minerals processing, pharmaceuticals or the environment.