SBE-β-CD (Sulfobutylether-β-Cyclodextrin)|182410-00-0|安捷凯

Background

SBE-β-CD, as a chemically modified β-CD, is a sulfobutylether β-cyclodextrin derivative. It always used as an excipient or a formulating agent to increase the solubility of poorly soluble agents.^[1] SBE-β-CD is used for enhancing the aqueous solubility of lipophilic drugs. And SBE-β-CD is very safe.^[2] Because of SBE-beta-CD has polyanionic nature, SBE-beta-CD interacts very well with neutral drugs to facilitate solubility and chemical stability.^[3]

In vitro, the solubility of nimodipine in the presence of SBE-β-CD increased more than in the presence of HP-β-CD in distilled water. Nimodipine has more affinity because of the highest K1:1 value exhibited by SBE-β-CD,which be ascribed to the presence of the four-carbon butyl chain coupled with repulsion of the end group negative charges which allows for an “extension” of the hydrophobic region of the CD cavity.^[4] At 400 mM SBE-β-CD concentration, the solubility of progesterone was ~7000-fold greater than its intrinsic solubility, aided by the formation of SBE-β-CD-progesterone complex. In addition, to prevent the displacement of progesterone from the complex by gastrointestinal contents, it needs to optimize the progesterone oral formulations by increasing the levels of SBE-β-CD in the formulation.^[5]

In vivo efficecy test it shown that the SBE-β-CD (128 M?1) had a higher solubilizing ability than that of HP-β-CD (79 M?1) suggesting suggest that a simple mixing of SD-CS and SBE-β-CD can be potentially useful for the controlled release of a medicine for the continuous treatment of hypertension. In vivo absorption of the drug after oral administration to rats indicated the slow release characteristics of the SD-CS/SBE-β-CD composite in vitro.^[6]

参考文献:
[1].Fukuda M, et al. Influence of sulfobutyl ether beta-cyclodextrin (Captisol) on the dissolution properties of a poorly soluble drug from extrudates prepared by hot-melt extrusion. Int J Pharm. 2008 Feb 28;350(1-2):188-96.
[2].Parvathaneni V, et al. Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes. Int J Mol Sci. 2021 Apr 30;22(9):4783.
[3].Stella VJ, He Q. Cyclodextrins. Toxicol Pathol. 2008 Jan;36(1):30-42.
[4].Semcheddine F, et al. Effects of the Preparation Method on the Formation of True Nimodipine SBE-β-CD/HP-β-CD Inclusion Complexes and Their Dissolution Rates Enhancement. AAPS PharmSciTech. 2015 Jun;16(3):704-15.
[5].Shankar VK, et al. Optimization of sulfobutyl-ether-β-cyclodextrin levels in oral formulations to enhance progesterone bioavailability. Int J Pharm. 2021 Mar 1;596:120212.
[6].Anraku M, et al. Design and Evaluation of An Extended-Release Olmesartan Tablet Using Chitosan/Cyclodextrin Composites. Pharmaceutics. 2019 Feb 15;11(2):82.

SBE-β-CD 是一种经过化学修饰的 β-CD，是一种磺丁基醚 β-环糊精衍生物。它常被用作赋形剂或制剂，以增加难溶性药物的溶解度。^[1] SBE-β-CD用于增加亲脂性药物的水溶性。并且SBE-β-CD非常安全。^[2]由于SBE-β-CD具有聚阴离子性质，SBE-β-CD与中性药物的相互作用非常好，有利于溶解性和化学稳定性。<支持>[3]

在体外，尼莫地平在 SBE-β-CD 存在下的溶解度比 HP-β-CD 在蒸馏水中的溶解度增加更多。尼莫地平具有更高的亲和力，因为 SBE-β-CD 表现出最高的 K1:1 值，这归因于四碳丁基链的存在加上端基负电荷的排斥，从而允许"延伸" CD 腔的疏水区域。^[4] 在 400 mM SBE-β-CD 浓度下，黄体酮的溶解度比其固有溶解度高约 7000 倍，这得益于 SBE- 的形成β-CD-孕酮复合物。此外，为防止黄体酮被胃肠道内容物从复合物中置换出来，需要通过增加制剂中SBE-β-CD的含量来优化黄体酮口服制剂。^[5]\n

体内功效测试表明，SBE-β-CD (128 M-1) 具有比 HP-β-CD (79 M-1) 更高的增溶能力，表明 SD- CS 和 SBE-β-CD 可用于控制药物释放以持续治疗高血压。 SD-CS/SBE-β-CD复合物在大鼠口服给药后的体内吸收表明了该复合物在体外的缓释特性。^[6]

Protocol

Animal experiment:

Rats[3] A 300 g rat is administered with 1 mL of a 0.1 M SBE-β-CD solution containing 5.64 mg of Compound 1, and assuming an extracellular volume of 90 mL, less than 0.1% of the complex would rapidly dissociate due to the initial effects of dilution. This calculation, combined with the changing blood to plasma ratio in the presence of SBE-β-CD, provides a reasonable explanation for the observed differences in the blood and plasma profiles of Compound 1 after intravenous administration in either the cyclodextrin or cyclodextrin-free formulations. After IV administration of the cyclodextrin formulation, Compound 1 would initially be prevented from distributing into erythrocytes thereby resulting in a whole blood to plasma ratio of less than one. Subsequently, clearance of SBE-β-CD from the circulation would lead to changes in the complexation equilibrium such that the unbound fraction of Compound 1 would increase, thereby reestablishing normal blood to plasma partitioning (i.e. in favour of whole blood) and clearance.

参考文献:

[1]. Fukuda M, et al.Influence of sulfobutyl ether beta-cyclodextrin (Captisol) on the dissolution properties of a poorly soluble drug from extrudates prepared by hot-melt extrusion.Int J Pharm. 2008 Feb 28;350(1-2):188-196
[2]. Lockwood SF, et al. Improved aqueous solubility of crystalline astaxanthin (3,3'-dihydroxy-beta, beta-carotene-4,4'-dione) by Captisol (sulfobutyl ether beta-cyclodextrin). J Pharm Sci. 2003 Apr;92(4):922-926.
[3]. Charman SA, et al. Alteration of the intravenous pharmacokinetics of a synthetic ozonide antimalarial in the presence of a modified cyclodextrin. J Pharm Sci. 2006 Feb;95(2):256-67
[4]. Fettiplace MR, et al. Cardiac depression induced by cocaine or cocaethylene is alleviated by lipid emulsion more effectively than by sulfobutylether-β-cyclodextrin. Acad Emerg Med. 2015 May;22(5):508-17