Preparation And Characterization Of Meloxicam Solid Dispersions And Tablets

Meloxicam(MLX)is used to the treatment of rheumatoid arthritis,painful osteoarthritis and other postoperative pains.It is a selective COX-2 inhabitor,which has superior effect than other anti-inflammatory drugs such as piroxicam and diclofenac.However,the solubility and the oral absorption rate of meloxicam is slow,which limits the onset of drug action.Therefore,improving the solubility and dissolution behavior is the key to exert its pharmacological effects.In this paper,meloxicam was used as a model drug to investigate the miscibility of drug-polymer,the solubilization ability,and the inhibition effect of polymers on the supersaturated drug solution.These researches lay a foundation for the preparation of solid dispersions and screening of carrier materials in the future.In this study,the meloxicam solid dispersion was prepared by solvent evaporation method.The optimum mass ratio between drug and polymer was 1:5,and the solid dispersions with better dissolution results were MLX-PVP K30(1:5,w/w),MLX-PVP VA(1:5,w/w)and MLX-SLP(1:5,w/w).It was found that meloxicam was converted into amorphous form in three kinds of solid dispersions by SEM,DCS,XRD and IR,and there was hydrogen bonding interaction.According to theoretical calculations of Hansen solubility parameter,the PVP K30,PVP VA and SLP were miscible with MLX in a decreasing order of PVP VA>PVP K30>SLP.Further experimental research indicated that,the PVP K30 had inferior solubilization capacity and the relatively short supersaturation time.In comparison,PVP VA and SLP had better performance to improve solubility and inhibit crystallization.In addition,the stability experiment results indicated that MLX-PVP K30 and MLX-SLP appeared evident crystallization,whereas,the MLX-PVP VA was comparatively stable.Therefore,it was demonstrated that MLX-PVP VA(1:5,w/w)was the best amorphous solid dispersion.And the subsequent pharmacokinetic study further illustrated that MLX-PVP VA(1:5,w/w)showed larger Cmax(3.25 times),AUC(0-?)(2.93 times)and the peak concentration time was 3 hours ahead of pure MLX,which achieved rapid oral absorption and improved bioavailability.The Optimized meloxicam solid dispersion,MLX-PVP VA(1:5,w/w)was compressed into tablets by wet granulation filler.After evaluating the quality of the tablets,better prescription and process were selected.The difference in tablet weight,hardness,friability,content uniformity,dissolution,etc.all met the requirements,and the sample was stable under high temperature(60?)conditions,and slightly hygroscopic under high humidity(RH 92.5%).In summary,the amorphous solid dispersion technology could effectively increase the dissolution and bioavailability of poorly soluble drugs,and the choice of carriers was a key factor for the successful preparation.In this study,PVP VA could effectively maintain the supersaturation,achieving the "spring with parachute"phenomenon,and the crytal transformation was not occur in the stability experiment.Studies on meloxicam solid dispersion tablets showed that MLX-PVP VA(1:5,w/w)could be used in new low-dose formulations and was expected to develop new formulations.