Development of Tramadol Microparticles by Non-solvent Addition Method and their In Vitro Characterization

New formulations of microparticles for Tramadol HCl (TmH) controlled-release were developed and evaluated. These microparticles with controlled-release characteristics were prepared by non-solvent addition technique. Ethyl cellulose (EC) a hydrophobic polymer was employed to control and extend the drug release process. Dichloromethane (DCM) was employed as solvent for polymer and paraffin oil as non-solvent which induced phase separation. Microparticles of different polymer concentrations M1 (1:1), M2 (1:2) and M3 (1:3) were prepared. Among all these formulations, M3 presented superior and desirable characteristics, i.e., 79% entrapment efficiency, good micromeritic properties, smooth morphology, and more sustained effect on cumulative release. Zero order, first order, Higuchi, Hixson-Crowell, and Korsmeyer-Peppas kinetic models were applied to assess the mechanism and pattern of drug release from microparticles. Release of TmH was best fitted to Higuchi model because it presented highest values of correlation coefficient (R2 = 0.981) followed by zero-order kinetic model (R2 = 0.899). FTIR, XRD, and DSC analyses ensured the chemical stability and integrity of TmH and EC in M3 as no new bands were detected in FTIR spectra. Moreover the XRD patterns of TmH showed its reduced crystallinity and endothermic peak was observed at the glass transition temperature of EC in DSC spectra. M3 sample was kept at 40؛C/75% RH for three months and its stability was evaluated by determining sample s in vitro release profile and drug assay. The effect of accelerated environment on its stability was not significant.