Purpose

The classic liquisolid technique is used to enhance the dissolution rate of poorly water-soluble drugs, but in some cases, it is impossible to reach the desired dissolution rate using this technique alone. Therefore, a novel approach using a combination of ball milling and liquisolid technology was investigated to improve the dissolution rate for celecoxib.

Methods

First, celecoxib was dispersed in a liquid vehicle (PEG 200), then ground in a ball mill for 3 h. Other excipients, including PVP, microcrystalline cellulose as the carrier powder, and silica as the coating material, were added to the mortar. Dissolution testing was carried out in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF) media. The effects of aging on the hardness and dissolution profile were also studied. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) was used to identify changes in the crystallinity or complex formation.

Results

The novel formulations showed a higher dissolution rate than the conventional tablet or classic liquisolid formulations. Aging did not affect the hardness and dissolution profiles of the liquisolid compacts. The DSC and XRD results suggested that the enhanced dissolution rate is not caused by the formation of any complexes and reduction in crystallinity degree may contribute to the dissolution enhancement. The enhanced dissolution rate is attributed to the elevated specific surface area of the drug in the liquisolid state.

Conclusion

The results showed that liquisolid technology combined with ball milling is an efficient tool for enhancing the dissolution of poorly water-soluble drugs.

中文翻译：

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结合液固和共磨技术提高塞来昔布的溶出度

目的

经典的液固技术用于提高水溶性差的药物的溶出度，但在某些情况下，仅使用该技术无法达到所需的溶出度。因此，研究了一种结合球磨和液固技术的新方法，以提高塞来昔布的溶出度。

方法

首先，将塞来昔布分散在液体载体（PEG 200）中，然后在球磨机中研磨 3 小时。其他赋形剂，包括 PVP、作为载体粉末的微晶纤维素和作为涂层材料的二氧化硅，被添加到研钵中。在模拟肠液 (SIF) 和模拟胃液 (SGF) 介质中进行溶出度测试。还研究了老化对硬度和溶出曲线的影响。X 射线衍射 (XRD) 和差示扫描量热法 (DSC) 用于识别结晶度或复合物形成的变化。

结果

与传统片剂或经典液固体制剂相比，新制剂显示出更高的溶出度。老化不影响液态固体压块的硬度和溶解曲线。DSC 和 XRD 结果表明溶出速率的提高不是由任何络合物的形成引起的，结晶度的降低可能有助于溶出度的提高。提高的溶出速率归因于液态药物的比表面积增加。

结论

结果表明，液固技术与球磨相结合是提高难溶性药物溶出度的有效工具。