Introduction

In previous studies carried out in our laboratory, a bile acid (BA) formulation exerted a hypoglycaemic effect in a rat model of type-1 diabetes (T1D). When the antidiabetic drug gliclazide (G) was added to the bile acid, it augmented the hypoglycaemic effect. In a recent study, we designed a new formulation of gliclazide-cholic acid (G-CA), with good structural properties, excipient compatibility and exhibits pseudoplastic-thixotropic characteristics. The aim of this study is to test the slow release and pH-controlled properties of this new formulation. The aim is also to examine the effect of CA on G release kinetics at various pH values and different temperatures.

Method

Microencapsulation was carried out using our Buchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared: G-SA (control) and G-CA-SA (test) at a constant ratio (1:3:30), respectively. Microcapsules were examined for efficiency, size, release kinetics, stability and swelling studies at pH 1.5, pH 3, pH 7.4 and pH 7.8 and temperatures of 20 and 30 °C.

Results

The new formulation is further optimised by the addition of CA. CA reduced microcapsule swelling of the microcapsules at pH 7.8 and pH 3 at 30 °C and pH 3 at 20 °C, and, even though microcapsule size remains similar after CA addition, percent G release was enhanced at high pH values (pH 7.4 and pH 7.8, p < 0.01).

Conclusion

The new formulation exhibits colon-targeted delivery and the addition of CA prolonged G release suggesting its suitability for the sustained and targeted delivery of G and CA to the lower intestine.

中文翻译：

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高级格列齐特-胆酸制剂的稳定性和释放动力学：人工细胞微囊化在抗糖尿病药物的缓释靶向口服给药中的应用。

介绍

在我们实验室之前进行的研究中，胆汁酸 (BA) 制剂在 1 型糖尿病 (T1D) 大鼠模型中发挥了降血糖作用。当将抗糖尿病药物格列齐特 (G) 添加到胆汁酸中时，它会增强降血糖作用。在最近的一项研究中，我们设计了一种新的格列齐特-胆酸 (G-CA) 配方，具有良好的结构特性、赋形剂相容性和假塑性触变特性。本研究的目的是测试这种新配方的缓释和 pH 控制特性。目的还在于检查 CA 在不同 pH 值和不同温度下对 G 释放动力学的影响。

方法

使用我们实验室开发的基于 Buchi 的微囊化系统进行微囊化。使用海藻酸钠 (SA) 聚合物制备两种配方：分别为恒定比例 (1:3:30) 的 G-SA（对照）和 G-CA-SA（测试）。在 pH 1.5、pH 3、pH 7.4 和 pH 7.8 以及 20 和 30 °C 的温度下检查微胶囊的效率、大小、释放动力学、稳定性和溶胀研究。

结果

新配方通过添加 CA 进一步优化。CA 在 pH 7.8 和 30 °C 下的 pH 3 和 20 °C 下的 pH 3 下降低了微胶囊的微胶囊溶胀，并且，即使在添加 CA 后微胶囊尺寸保持相似，在高 pH 值（pH 7.4 和pH 7.8，p  < 0.01)。

结论

新配方表现出结肠靶向递送和 CA 延长 G 释放的添加，表明其适用于将 G 和 CA 持续和靶向递送至下肠。