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接触角测量:一种理解含表面活性剂的乙基纤维素片增加药物溶出机制的新方法,并探讨其接触角与溶出行为之间的关系。

Contact Angle Measurements: an Alternative Approach Towards Understanding the Mechanism of Increased Drug Dissolution from Ethylcellulose Tablets Containing Surfactant and Exploring the Relationship Between Their Contact Angles and Dissolution Behaviors.

机构信息

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Benxi, 117004, People's Republic of China.

School of Pharmacy, Shenyang Pharmaceutical University, Benxi, 117004, People's Republic of China.

出版信息

AAPS PharmSciTech. 2018 May;19(4):1582-1591. doi: 10.1208/s12249-018-0975-6. Epub 2018 Feb 27.

Abstract

The addition of surfactant in tablet was a well-defined approach to improve drug dissolution rate. While the selected surfactant played a vital role in improving the wettability of tablet by medium, it was equally important to improve the dissolution rate by permeation effect due to production of pores or the reduced inter-particle adhesion. Furthermore, understanding the mechanism of dissolution rate increased was significant. In this work, contact angle measurement was taken up as an alternative approach for understanding the dissolution rate enhancement for tablet containing surfactant. Ethylcellulose, as a substrate, was used to prepare tablet. Four surfactants, sodium dodecyl sulfate (SDS), sodium dodecylbenzenesulfonate (SDBS), dodecyltrimethylammonium bromide (DTAB), and sodium lauryl sulfonate (SLS), were used. Berberine hydrochloride, metformin hydrochloride, and rutin were selected as model drugs. The contact angle of tablet in the absence and presence of surfactant was measured to explore the mechanism. The dissolution test was investigated to verify the mechanism and to establish a correlation with the contact angle. The result showed that the mechanism was the penetration effect rather than the wetting effect. The dissolution increased with a reduction in the contact angle. DTAB was found to obtain the highest level of dissolution enhancement and the lowest contact angle, while SDS, SDBS, and SLS were found to be the less effective in both dissolution enhancement and contact angle decrease. Therefore, contact angle was a good indicator for dissolution behavior besides exploring the mechanism of increased dissolution, which shows great potential in formula screening.

摘要

在片剂中添加表面活性剂是一种明确的方法,可以提高药物的溶出速率。虽然所选的表面活性剂在改善介质对片剂的润湿性方面起着至关重要的作用,但通过渗透作用提高溶出速率同样重要,因为它可以产生孔隙或减少颗粒间的黏附。此外,了解溶出速率提高的机制也很重要。在这项工作中,接触角测量被用作理解含表面活性剂片剂溶出速率增强的替代方法。乙基纤维素作为基质,用于制备片剂。使用了四种表面活性剂,十二烷基硫酸钠(SDS)、十二烷基苯磺酸钠(SDBS)、十二烷基三甲基溴化铵(DTAB)和十二烷基硫酸钠(SLS)。盐酸小檗碱、盐酸二甲双胍和芦丁被选为模型药物。测量了片剂在有无表面活性剂存在下的接触角,以探讨其机制。进行了溶出试验,以验证该机制并与接触角建立相关性。结果表明,该机制是渗透作用而不是润湿作用。随着接触角的降低,溶出度增加。DTAB 被发现具有最高的溶出增强水平和最低的接触角,而 SDS、SDBS 和 SLS 则被发现对溶出增强和接触角降低都不太有效。因此,接触角除了可以探索溶出增加的机制外,还是一种很好的溶出行为指标,在配方筛选中具有很大的潜力。

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