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

Eur J Pharm Biopharm. 2008 Nov;70(3):861-8. doi: 10.1016/j.ejpb.2008.07.006. Epub 2008 Jul 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylates / chemistry*
  • Anilides / chemistry*
  • Anti-HIV Agents / chemistry*
  • Chemistry, Pharmaceutical
  • Drug Carriers*
  • Furans / chemistry*
  • Kinetics
  • Polyethylene Glycols / chemistry
  • Polymers / chemistry*
  • Powders
  • Solubility
  • Surface-Active Agents / chemistry*
  • Technology, Pharmaceutical / methods
  • Thioamides
  • Transition Temperature
  • Vitamin E / analogs & derivatives*
  • Vitamin E / chemistry

Substances

  • Acrylates
  • Anilides
  • Anti-HIV Agents
  • Drug Carriers
  • Eudragit E100
  • Furans
  • Polymers
  • Powders
  • Surface-Active Agents
  • Thioamides
  • Vitamin E
  • Polyethylene Glycols
  • UC-781
  • tocophersolan