Combining Liquisolid and Co-grinding Techniques to Enhance the Dissolution Rate of Celecoxib

Abstract

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.