Dissolution enhancement of the anti-HIV drug UC 781 by formulation in a ternary solid dispersion with TPGS 1000 and Eudragit E100

Abstract

The present research deals with the improvement of the dissolution properties of the anti-HIV drug UC 781. A ternary solid dispersion consisting of a high amount of TPGS 1000 and exhibiting good powder properties with respect to flowability was developed. Eudragit E100 was selected as a polymer based on supersaturation studies. DSC analysis of solid dispersions containing drug doses from 0 to 80% w/w revealed eutectic phase behaviour of the ternary TPGS 100–Eudragit E100–UC 781 mixture. The release of UC 781 in a medium simulating the gastrointestinal lumen was markedly enhanced, reaching a release of 70% w/w after 4 h. XRD results pointed to the presence of crystalline drug in the solid dispersion. The presence of UC 781 in the dispersion had an influence on the TPGS 1000–Eudragit E100 carrier, favoring folding of the polyethylene glycol chains in TPGS 1000. Moreover, the addition of UC 781 to the binary polymer–surfactant mixture was physically expressed by an increase in fluidity of the samples up to a drug load of 50% w/w. NMR was used to investigate this phenomenon, revealing a shielding and/or deshielding effect of the carrier on aromatic C atoms and methyl groups in UC 781. Polyethylene glycol chains present in TPGS 1000 seemed to play a role in this process. In addition, combining UC 781 with the TPGS 1000–Eudragit E100 mixture led to the appearance of TPGS 1000 clusters with a glass transition temperature well below the T g’s of the pure compounds.