Study on Effect of Solvents and Non-Solvents on Release of Tramadol Hydrochloride from Microspheres Prepared by Various Coacervation Phase Separation Technique

Abstract

The objective of the study was to determine the effect of solvents like acetone, dimethyldigol, 1,4-dioxan and non-solvents like n-hexane and chloroform on microencapsulation of tramadol hydrochloride. The microspheres were prepared by following coacervation phase separation using various non- aqueous solvents and non-solvents like solvent evaporation and non-solvent addition method with release rate retarding cellulose polymers. Microspheres were characterized for the particle size distribution, wall thickness by scanning electron microscopy (SEM), angle of repose, bulk density, percent drug content, entrapment efficiency and in vitro dissolution studies. Drug excipient compatibility was determined by FTIR and DSC. Accelerated stability studies were also carried out following ICH Guidelines. SEM revealed that microspheres were found spherical, free flowing and porous. The wall thickness and entrapment efficiency was found in between 78.51μ to 108.10μ, 61.92% to 95.54 % respectively. The drug release was extended maximum upto 12hours with cellulose acetate using 1-4 dioxan as solvent and upto 12 hours with cellulose acetate phthalate using 1,4-dioxan and dimethyldigol. FTIR and XRD spectra results showed tramadol hydrochloride was compatible with excipients. The curve fitting data revealed that the release followed first order kinetics and higuchi’s and peppas plots stated non-fickian and diffusion controlled. Dimethyldigol and 1,4 dioxan as solvent polymer effected over the size and release kinetics.