使用 pH 值变化法并加入十二种具有不同物理化学性质的稳定剂来提高格列齐特的溶解度。

Dissolution enhancement of gliclazide using pH change approach in presence of twelve stabilizers with various physico-chemical properties.

机构信息

Food and Drug Laboratory, Tehran, Iran.

出版信息

J Pharm Pharm Sci. 2009;12(3):250-65. doi: 10.18433/j31p4p.

DOI:10.18433/j31p4p

PMID:20067702

Abstract

PURPOSE

The micronization using milling process to enhance dissolution rate is extremely inefficient due to a high energy input, and disruptions in the crystal lattice which can cause physical or chemical instability. Therefore, the aim of the present study is to use in situ micronization process through pH change method to produce micron-size gliclazide particles for fast dissolution hence better bioavailability.

METHODS

Gliclazide was recrystallized in presence of 12 different stabilizers and the effects of each stabilizer on micromeritic behaviors, morphology of microcrystals, dissolution rate and solid state of recrystallized drug particles were investigated.

RESULTS

The results showed that recrystallized samples showed faster dissolution rate than untreated gliclazide particles and the fastest dissolution rate was observed for the samples recrystallized in presence of PEG 1500. Some of the recrystallized drug samples in presence of stabilizers dissolved 100% within the first 5 min showing at least 10 times greater dissolution rate than the dissolution rate of untreated gliclazide powders. Micromeritic studies showed that in situ micronization technique via pH change method is able to produce smaller particle size with a high surface area. The results also showed that the type of stabilizer had significant impact on morphology of recrystallized drug particles. The untreated gliclazide is rod or rectangular shape, whereas the crystals produced in presence of stabilizers, depending on the type of stabilizer, were very fine particles with irregular, cubic, rectangular, granular and spherical/modular shape. The results showed that crystallization of gliclazide in presence of stabilizers reduced the crystallinity of the samples as confirmed by XRPD and DSC results.

CONCLUSION

In situ micronization of gliclazide through pH change method can successfully be used to produce micron-sized drug particles to enhance dissolution rate.

摘要

目的

由于高能量输入和晶格的破坏，研磨工艺的微米化会极大地降低药物的溶解速率，从而导致物理或化学不稳定性。因此，本研究的目的是通过 pH 值变化法原位微米化过程来制备米格列奈结晶，以实现快速溶解，从而提高生物利用度。

方法

在 12 种不同稳定剂的存在下对格列齐特进行重结晶，研究了每种稳定剂对微细化行为、微晶形态、溶解速率和重结晶药物颗粒的固体状态的影响。

结果

结果表明，与未处理的格列齐特颗粒相比，重结晶样品的溶解速率更快，而在 PEG 1500 存在下重结晶的样品具有最快的溶解速率。一些存在稳定剂的重结晶药物样品在 5 分钟内完全溶解，其溶解速率至少比未处理的格列齐特粉末高 10 倍。微细化研究表明，通过 pH 值变化法的原位微米化技术能够产生更小的粒径和更高的表面积。结果还表明，稳定剂的类型对重结晶药物颗粒的形态有显著影响。未处理的格列齐特为棒状或矩形，而在稳定剂存在下生成的晶体，根据稳定剂的类型，为非常细的不规则、立方、矩形、粒状和球形/模块状颗粒。结果表明，在稳定剂存在下，格列齐特的结晶降低了样品的结晶度，这一结果通过 X 射线粉末衍射（XRPD）和差示扫描量热法（DSC）结果得到了证实。