Preparation and evaluation of enteric release naproxen microparticles by spherical crystallization technique

The objective of this study was to prepare and evaluate naproxen loaded enteric microparticles produced by spherical crystallization method. The method relies on the precipitation of the enteric polymer hydroxypropyl methyl cellulose phthalate (HPMCP), when its solution in an aqueous alkaline media are dropped into an acidic environment. Various manufacturing parameters, including polymer/naproxen ratio, the initial difference in temperature between solvent and non solvent (ΔT) and concentration of acid in non solvent were altered during the microparticle production. The effects of these changes on the micromeritic characteristics of microparticles and encapsulation efficiency were examined. The microparticles were also characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and x-ray diffractometry analyses. Dissolution studies were finally carried out to verify if the microparticles possessed gastroresistant characteristics. The growth of particle size and the spherical form of the agglomerates resulted in formation of products with good flow properties. Drug release studies showed that naproxen release from microparticles exhibited pH dependent profiles. Greater encapsulation efficiency was obtained by reduction the polymer/naproxen ratio and by increasing ΔT and concentration of acid in non solvent. The spherical crystallization technique used is simple and minimize the use of organic solvents, and can be useful tools in preparing naproxen enteric microparticles.