THERMAL-ANALYSIS AND DISSOLUTION AVAILABILITY OF SOLID DISPERSIONS OF TOLBUTAMIDE

We have established the phase diagram tolbutamide (TBM)-PEG 6000 and determined the eutectic composition 1/9 (w/w) in tolbutamide and melting temperature 56.2-degrees-C+/-0.3; no solid solution has been found. Negative mixing enthalpies of physical mixture (-2.5 J.g-1) and solid dispersions coprecipitate (-3.9 J.g-1) melt (-9.9 J.g-1) for eutectic composition involve the existence of interactions between drug and carrier. We have determined the dissolution kinetics: amount % dissolved (10 min) 65.87+/-0.55 (physical mixture), 78.02+/-0.02 (coprecipitate), 99.90+/-0.10 (melt). We have observed a good agreement between dissolution kinetics and mixing enthalpies data.