Purpose

To formulate multiparticulate controlled-release alginate-gelatin (AL-GL) beads in order to modify gliclazide (GLZ) release rate.

Methods

AL-GL beads were prepared using different glutaraldehyde concentrations and dried using either air or freeze-drying method. For comparison, calcium alginate beads (AL-beads) were prepared at different temperatures. Drug incorporation efficiency, beads swelling%, drug release rate, and kinetics in gradient conditions (USP Apparatus-4) were studied. Selected AL-GL beads, as a test formulation (T), were in-vivo compared with Diamicron® 80 mg conventional tablet (R).

Results

AL-beads curing temperature was inversely proportional to GLZ incorporation efficiency and directly proportional to beads swelling%. GLZ release from AL-beads was slow in 0.1 N HCl and very fast in pH 7.4. In case of AL-GL beads, GLZ incorporation efficiency and swelling% were inversely proportional to glutaraldehyde concentration. AL-GL beads showed zero-order release of GLZ for up to 11 h. Scanning electron microscope (SEM) images of the freeze-dried beads showed a highly porous surface. Differential scanning calorimetry (DSC) and Fourier transform infra-red (FT-IR) studies indicated an interaction between alginate and gelatin due to crosslinking, while FT-IR indicated the absence of chemical interaction with GLZ. The relative bioavailability (T/R) was 97.57, 138.34, and 143.53%, for C_max, AUC_0–72, and AUC_0–∞, respectively. T_max of T was significantly higher than R.

Conclusion

AL-GL beads could represent promising delivery systems for modulating GLZ release rate and minimizing the variation in its absorption.

中文翻译：

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利用多颗粒药物传递系统调节格列齐特的释放和生物利用度

目的

配制多颗粒控释藻酸盐-明胶（AL-GL）珠粒，以改善格列齐特（GLZ）的释放速率。

方法

使用不同的戊二醛浓度制备AL-GL珠粒，并使用空气或冷冻干燥法进行干燥。为了比较，在不同温度下制备藻酸钙珠（AL-珠）。研究了药物掺入效率，珠溶胀％，药物释放速率和梯度条件下的动力学（USP Apparatus-4）。与80 mg常规片剂（R）相比，将选定的AL-GL珠作为测试制剂（T）进行了体内实验。

结果

AL珠的固化温度与GLZ的掺入效率成反比，与珠溶胀％成正比。在0.1 N HCl中，AL珠中的GLZ释放缓慢，而在pH 7.4中，释放非常快。对于AL-GL珠，GLZ的掺入效率和溶胀％与戊二醛浓度成反比。AL-GL珠粒显示GLZ零级释放长达11小时。冷冻干燥的珠的扫描电子显微镜（SEM）图像显示出高度多孔的表面。差示扫描量热法（DSC）和傅立叶变换红外（FT-IR）研究表明，由于交联，藻酸盐和明胶之间存在相互作用，而FT-IR表明与GLZ没有化学相互作用。对于C _max，AUC ，相对生物利用度（T / R）为97.57、138.34和143.53％_0–72和AUC _0–∞。T的T _max显着高于R。

结论

AL-GL磁珠可以代表有前途的传递系统，用于调节GLZ释放速率并最大程度地减少其吸收变化。