title: 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 4h. 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.
authors.affiliation: Laboratory of Pharmacotechnology and Biopharmacy, Catholic University of Leuven, Leuven, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Goddeeris
authors.forename: T
authors.initials: T
authors.lastname: Willems
authors.forename: K
authors.initials: K
authors.lastname: Houthoofd
authors.forename: J A
authors.initials: JA
authors.lastname: Martens
authors.forename: G
authors.initials: G
authors.lastname: Van den Mooter
mesh_terms: D000179:Acrylates / Q000737:chemistry*; D000813:Anilides / Q000737:chemistry*; D019380:Anti-HIV Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D005663:Furans / Q000737:chemistry*; D007700:Kinetics; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011208:Powders; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods; D013854:Thioamides; D044366:Transition Temperature; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D000179:Acrylates; D000813:Anilides; D019380:Anti-HIV Agents; D004337:Drug Carriers; C477020:Eudragit E100; D005663:Furans; D011108:Polymers; D011208:Powders; D013501:Surface-Active Agents; D013854:Thioamides; D014810:Vitamin E; D011092:Polyethylene Glycols; C100668:UC-781; C014225:tocophersolan