Thermal properties and eutectic behaviour of dapivirine in combination with steroid hormones and other antiretrovirals

Karl Malcolm, Clare McCoy, Diarmaid Murphy, Peter Boyd, Sandeep Kumar, Susan Fetherston, Andrew Brimer, Jonathon Holt, Brid Devlin, Wendy Blanda, Jeremy Nuttall, Chris Gilmour

Research output: Contribution to conferencePosterpeer-review

379 Downloads (Pure)

Abstract

Background: Combination drug products can display thermal behaviour that is more complex than for the corresponding single drug products. For example, the contraceptive vaginal ring (VR) Nuvaring contains a eutectic (lowest melting) composition of etonogestrel (ETN) and ethinyl estradiol. Here we report the predisposition of dapivirine (DPV) to form reduced melting/eutectic mixtures when combined with other contraceptive hormones and antiretrovirals, and discuss the implications for development of combination microbicide and multipurpose prevention technology (MPT) products.
Methods: Binary mixtures of DPV with darunavir (DRV), levonorgestrel (LNG), ETN or maraviroc (MVC) were prepared either by physical mixing or by solvent evaporation. Selected binary mixtures were also incorporated into silicone elastomer (SE) VR devices. Thermal behavior of the mixtures was analyzed using differential scanning calorimetry (DSC) operating in standard heating ramp mode (10 °C/min). DSC data were used to construct two component phase diagrams for each binary system.
Results: Drug mixtures typically showed reduced melting transitions for both drug components, with clear evidence for a eutectic mixture at a well-defined intermediate composition. Eutectic temperatures and compositions for the various mixtures were: 40% DPV / 60% ETN - 170°C; 25% DPV / 75% MVC - 172°C; 65% DPV / 35% LNG - 192°C. In each case, the eutectic composition was also detected when the drug mixtures were incorporated into SE VRs. For the DPV/DRV system, the thermal behaviour is complicated by desolvation from the darunavir ethanolate polymorph.
Conclusions: When DPV is combined with small molecular weight hydrophobic drugs, the melting temperature for both drugs is typically reduced to a degree dependent on the composition of the mixture. At specified compositions, a low melting eutectic system results. The formation of eutectic behavior in binary drug systems needs to be carefully characterised in order to define product performance and drug release.
Original languageEnglish
Publication statusPublished - 29 Oct 2014
EventHIV R4P - HIV Research for Prevention - Cape Town, South Africa
Duration: 28 Oct 201431 Oct 2014
http://hivr4p.org/

Conference

ConferenceHIV R4P - HIV Research for Prevention
CountrySouth Africa
CityCape Town
Period28/10/201431/10/2014
Internet address

Keywords

  • dapivirine
  • vaginal ring
  • thermal
  • maraviroc
  • steroids
  • eutectic

Fingerprint

Dive into the research topics of 'Thermal properties and eutectic behaviour of dapivirine in combination with steroid hormones and other antiretrovirals'. Together they form a unique fingerprint.

Cite this