Effects of some process parameters on the niflumic acid controlled release polymeric microspheres: Optimization using designs of experiments

Microparticles charged by niflumic acid and based on cellulose derivatives as polymeric matrices, that is, ethylcellulose (EC) and mixtures of EC and hydroxypropylmethylcellulose (HPMC), were elaborated using microencapsulation by emulsion-solvent evaporation technique. The niflumic acid is considered as a poorly water soluble drug, so the main objective of the paper is to use designs of experiment in order to prepare new solid formulations with a large range of size for the drug dissolution enhancement. The possible drug-polymer interaction was investigated by Fourier transform-infrared spectroscopy, X-ray diffraction, and differential scanning calorimetric analysis. Some of the process variables, namely, the stirring speed of emulsion, the emulsifier concentration, and the EC:HPMC ratio, were selected and varied. Their main and interactive effects on the microparticles' characteristics were obviously evaluated and discussed using Minitab software 16.1. The obtained microparticles' size (d(10)) ranged from 196 to 796 mu m, and the drug entrapment reached 45% in some formulations. The drug dissolution results showed that the Higuchi's release constant varied from 0.011 to 0.067 min(-1/2) and was enhanced especially when the HPMC concentration was increased.