Formulation development of solid dispersions of bosentan using gelucire 50/13 and poloxamer 188

Abstract

The objectives of the present research work are to improve the solubility and dissolution rate of bosentan. Solid dispersions of bosentan were prepared by fusion method by using two selected hydrophilic meltable carriers vis-à-vis gelucire 50/13 and poloxamer 188. Sylysia 350 was used as an adsorbent. Solid dispersions were evaluated for solubility, phase solubility, flowability, compressibility, Fourier transform infrared spectra (FT-IR), differential scanning calorimetry (DSC). Solubility studies showed 8 and 10 fold increase in solubility for gelucire 50/13 and poloxamer 188 based solid dispersions respectively. The Gibbs free energy ΔGtr° values were all negative for gelucire 50/13 (0, 0.1, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8 and 10 % w/v) and poloxamer 188 (0, 0.1, 0.25, 0.5, 0.75 and 1 % w/v) indicating spontaneous nature of solubilisation. FT-IR and DSC spectra showed that drug and carriers are compatible with each other. Solid dispersions exhibiting highest solubility were compressed into immediate release tablets by using sodium starch glycolate as superdisintegrant. In vitro dissolution studies, exhibited more than 90 % drug dissolution in 1 h. Gelucire 50/13 and poloxamer 188 plays a significant role in enhancement of drug solubility and dissolution. The adsorbent, sylysia 350 may be used to impart good flow and compressibility to solid dispersions. Among the two carriers, poloxamer 188 exhibited better solubility and dissolution enhancement potential.