Combination of liquisolid and co-grinding technologies for enhancing dissolution rate of celecoxib

Abstract

Introduction: Celecoxib is a poorly solubale, highly permeable drug and its oral absorption is often controlled by dissolution rate in the gastrointestinal track. There are several techniques to enhance the dissolution of poorly soluble drugs. The most promising method for this mean is the formation of liquidsolid tablets. In classic method of liquisolid technique, higher dissolution rate was not obtained in previous study. Goals: new concept was examined in this research for obtaining better dissolution rate of celecoxib. For this mean combination of ballmilling and liuqisolid technology was investigated. Methods: Liquid medications were prepared by dispersing the drug in liquid vehicle (PEG200) and grinding them in ballmill for 3 hours. After that, other excipients like PVP, microcrystalline cellulose as the carrier powder, silica as the coating material were added. Direct compression tablets were prepared using mentioned exipiens except non volatile solvent. Then dissolution test were done in SIF and SGF media. The effect of aging on hardness and dissolution profile was also studied. XRD and DSC thermograms were used for study of any cristallinity change or complex formation. Results: Prepared compacts, had good properties in view of hardness and friability. These formulations showed higher dissolution rate than those of conventional tablet or classic liquisolid formulations. Aging had no effect of hardness and dissolution properties if prepared compacts. DSC and X-RAY finding suggested that the enhanced dissolution rate of celecoxib liquidsolid compacts is not due to the formation of any complex or any changes in crystallinity. Discussion: Obtained dissolution rate is due to enhanced special surface of drug to the medium in liquisolid state and also micronized drugs during ball mill process. Liquidsolid technique could be promising alternative technique to increase dissolution rate of water insoluble drugs without any change in crystallinity.