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以盐酸文拉法辛作为模型带电药物,将数学建模应用于海藻酸钠-壳聚糖聚电解质复合物以预测系统行为。

Application of mathematical modelling to alginate chitosan polyelectrolyte complexes for the prediction of system behavior with Venlafaxine HCl as a model charged drug.

作者信息

Ibrahim Howida K, Sorour Rania Mohamed Hassan, Salah Ad-Din Ibtehal

机构信息

Faculty of Pharmacy, Cairo University, Cairo, Egypt.

New Kasr El Ainy Teaching Hospital, Cairo University, Cairo, Egypt.

出版信息

Saudi Pharm J. 2022 Oct;30(10):1507-1520. doi: 10.1016/j.jsps.2022.07.013. Epub 2022 Aug 4.

Abstract

PURPOSE

This work aimed to develop and analyze the performance of chitosan/alginate polyelectrolyte complex (PEC). Multiple regression and Lab fit curve fitting were applied to derive empirical models for the prediction of zeta potential of plain systems as a function of alginate chitosan ratio. Venlafaxine-HCl was loaded as a model charged drug and empirical models for prediction of its release as a function of time were also derived.

METHODS

Coacervation method was used for the preparation of green PECs. Preliminary studies were conducted to optimize the preparation method. Pre-adjustment of the pH of alginate and chitosan sols enabled the formation of PECs at alginate/chitosan ratios starting from 1:9 to 9:1. On mixing of alginate and chitosan sols, equal volume dilution method produced spherical particles, while direct mixing method gave fibrous particles. Twenty-seven PECs nanoparticle formulae were prepared using nine alginate/chitosan ratios and three levels of total polymer concentrations.

RESULTS

Statistical analysis showed that Zeta potential of the nanoparticle was significantly dependent on alginate/chitosan ratio, while particle size was a function of total polymer concentration. Nine fiber formulae were prepared and evaluated for their appearance and zeta potential. Venlafaxine-HCl release followed anomalous transport mechanism. FT-IR and DSC studies confirmed complexation at the carboxylate and amine site at alginate and chitosan respectively.

CONCLUSION

Chitosan/alginate PECs were successfully obtained without a cross-linker and empirical equations were obtained to help finding the best composition for loading charged drugs and to predict their release profiles.

摘要

目的

本研究旨在开发并分析壳聚糖/海藻酸盐聚电解质复合物(PEC)的性能。应用多元回归和实验室拟合曲线拟合来推导经验模型,以预测普通体系的zeta电位与海藻酸盐/壳聚糖比例的函数关系。将盐酸文拉法辛作为模型带电药物载入,并推导了预测其释放与时间函数关系的经验模型。

方法

采用凝聚法制备绿色PEC。进行了初步研究以优化制备方法。对海藻酸盐和壳聚糖溶胶的pH进行预调节,使得在海藻酸盐/壳聚糖比例从1:9到9:1时能够形成PEC。在混合海藻酸盐和壳聚糖溶胶时,等体积稀释法产生球形颗粒,而直接混合法则产生纤维状颗粒。使用九种海藻酸盐/壳聚糖比例和三种总聚合物浓度水平制备了二十七个PEC纳米颗粒配方。

结果

统计分析表明,纳米颗粒的zeta电位显著依赖于海藻酸盐/壳聚糖比例,而粒径是总聚合物浓度的函数。制备了九个纤维配方并对其外观和zeta电位进行了评估。盐酸文拉法辛的释放遵循异常转运机制。傅里叶变换红外光谱(FT-IR)和差示扫描量热法(DSC)研究分别证实了海藻酸盐和壳聚糖在羧酸盐和胺位点处的络合。

结论

无需交联剂即可成功获得壳聚糖/海藻酸盐PEC,并获得了经验方程,以帮助找到载入带电药物的最佳组成并预测其释放曲线。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4eb5/9649359/322a7ba6f3b5/gr1.jpg

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