Hossein Dehghani, Azade Taheri* and Alireza Homayouni Pages 709 - 717 ( 9 )
Background: Meloxicam (MLX) is classified as NSAID that is used for the treatment of rheumatoid arthritis and osteoarthritis. Poor water solubility of MLX leads to its slow oral absorption and slow onset. Preparation of solid dispersion (SD) could improve the water solubility of poorly water soluble drugs. It has been demonstrated that orally disintegrating tablets (ODTs) show faster onset of action and could be more appropriate for the treatment of acute pain.Method: The purpose of this study is to improve the solubility of MLX through the preparation of its SD and then decrease the onset of action by preparation of ODTs from prepared SD. MLX SDs were prepared by solvent evaporation method. MLX, polyvinylpyrrolidone k30 (PVP k30), crospovidone and sodium lauryl sulfate (SLS) with different ratios were dispersed in molten menthol as solvent. Menthol was separated by freeze drying. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis approved amorphous form of MLX in SDs. Result: The optimum SD with highest saturation solubility in water (12.60±1.2 microgram/ml) which consists of MLX, PVP, crospovidone and SLS in a ratio of 1:1:1:0.03 was used for the preparation of MLX ODTs. ODTs were prepared by direct compression method and optimized by 23 factorial design. The effect of the superdisintegrant concentration, mannitol/avicel ratio and the level of compression force was evaluated on the disintegration time, hardness and percent of dissolved MLX after 30 min of prepared MLX ODTs. The optimized ODT formulation contained 10% superdisintegrant, mannitol and avicel a ratio of 2:1 compressed using a high level of compression force. Conclusion: Optimized ODT showed hardness (48±4.3 N) and friability (0.81±0.07%). This formulation provided rapid disintegration in 19±2 seconds of which 77.8±5.1% of drug was released within 30 minutes. The present study demonstrated an effective method for the preparation of suitable dosage form of MLX with improved solubility and onset of action.
Avicel, mannitol, meloxicam, orally disintegrating tablets, sodium lauryl sulfate (SLS), solid dispersion, superdisintegrant.
Novel Drug Delivery Systems Research Center, Department of Pharmaceutics, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Department of Pharmaceutics, Faculty of Pharmacy and Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Postal Code 81746-73461, Novel Drug Delivery Systems Research Center, Department of Pharmaceutics, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan