Crystallization of meloxicam in the presence of hydrophilic additives to tailor its physicochemical and pharmaceutical properties

Abstract

It is known that the presence of impurities can affect the morphology and properties of crystals. In this study, the effects of various hydrophilic additives including polyvinylpyrrolidone, polyethylene glycol 4000, Pluronics F68 and F127 were investigated to modify crystal properties of meloxicam microcrystals (a poorly-soluble anti-inflammatory drug) aimed to enhance its dissolution. Two different methods (cooling and anti-solvent precipitation) were employed to prepare meloxicam microcrystals in the presence of different additives. Scanning electron microscope, X-ray diffraction, infrared spectrophotometry and differential scanning calorimetry were used to study morphology and crystalline characteristics of the particles. Physicochemical properties of the engineered meloxicam namely particle size, solubility, wettability and dissolution behavior were also evaluated. Different additives used in both crystallization methods resulted in prismatic particles without any polymorphic transition. Although the employed crystallization techniques decreased the particle size, the most crystal growth inhibition was observed for the particles prepared by the anti-solvent precipitation method in the presence of Pluronics F127 and F68. The dissolution rate of all samples was improved compared to the untreated MLX. Relative dissolution and dissolution efficiency (DE120) of those crystals were increased up to 2.5 and 3.3-fold compared to the intact meloxicam, respectively. These improvements in the dissolution of meloxicam could be attributed to the smaller particle size, higher wettability, and modified crystal habit of meloxicam.