聚合物基质释放二氟尼柳的动力学研究

P. A. Mihajlova, A. A. Adamova, Y. Generalova, P. Snetkov, S. Morozkina
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摘要

简介二氟尼柳治疗心脏淀粉样变性的有效性已得到临床证实。然而,长期使用非甾体抗炎药会导致特有的副作用。因此,目前正在积极开发双氟尼沙的给药系统(包括外用型),以减少副作用并提高其生物利用度。研究活性物质二氟尼柳从透明质酸聚合物基质中释放的动力学。研究对象是主要物质浓度分别为 0.093%、0.14%、0.19% 和 0.25%的透明质酸中的二氟尼柳凝胶。采用反相高效液相色谱法进行定量检测,色谱柱为 Prontosil C18,120-5,75 × 2 mm,恒温温度为 40 °C。流出液为 pH 值为 3.0 的磷酸盐缓冲溶液(PBS)和乙腈(30:70),流速为 0.1 ml/min。在 230、270 和 310 nm 波长下检测洗脱液。在这项工作中,选择了一种方法(高效液相色谱法),并开发了一种测定 HA 基质中地氟尼萨的方法。与药物溶解相比,所研究的给药系统大大提高了二氟尼柳在水溶液中的溶解度。活性物质从基质中的释放是在 pH 值为 7.6 的磷酸盐缓冲溶液中进行的。实验开始 3 小时后,所有样品的释放率均超过 90%,大部分活性物质在 1 小时内释放。获得的数据表明,释放曲线是可生物降解基质和扩散控制给药系统的特征。使用 pH 值为 7.6 的 PBS 作为溶解介质可实现从 HA 中完全提取地氟尼柳。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Study of the Dynamics of Diflunisal Release from a Polymer Matrix
Introduction. The effectiveness of diflunisal in the treatment of cardiac amyloidosis has been clinically proven. Currently, only tablet forms of diflunisal are registered in the world, however, long-term use of NSAIDs leads to characteristic side effects. Therefore, delivery systems for diflunisal (including a form for external use) are now being actively developed to reduce side effects and improve its bioavailability.Aim. Research of the dynamics of release of the active substance diflunisal from the polymer matrix of hyaluronic acid.Materials and methods. The objects of the study are diflunisal gels in hyaluronic acid with a concentration of the main substance of 0.093, 0.14, 0.19 and 0.25 %. Quantitative determination was carried out by reverse-phase HPLC using a Prontosil C18, 120-5, 75 × 2 mm chromatographic column, thermostatically controlled at 40 °C. Eluent: phosphate buffer solution (PBS) with pH 3.0 and acetonitrile (30 : 70), flow rate 0.1 ml/min. Eluates were detected at wavelengths of 230, 270, 310 nm.Results and discussion. During the work, a method (HPLC) was selected and a method for determining diflunisal in a HA matrix was developed. The delivery system under study significantly increases the solubility of diflunisal in an aqueous solution compared to the dissolution of the substance. The release of the active substance from the matrices was carried out in a phosphate buffer solution with pH 7.6. The release rate for all samples exceeded 90 % after 3 hours after the start of the experiment, with most of the active substance released within an hour.Conclusion. The data obtained suggest that the release profile is characteristic of biodegradable matrices and diffusion-controlled delivery systems. Complete extraction of diflunisal from HA was achieved using PBS with pH 7.6 as a dissolution medium.
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