Formulation of fast disintegrating tablets of ternary solid dispersions consisting of TPGS 1000 and HPMC 2910 or PVPVA 64 to improve the dissolution of the anti-HIV drug UC 781.
Solid dispersion formulations made up of d-alpha-tocopheryl polyethylene glycol succinate 1000 (TPGS 1000) and polyvinyl pyrrolidone co-vinyl acetate 64 (PVPVA 64) or hydroxy propyl methyl cellulose 2910 (HPMC 2910) were developed in order to improve the dissolution of UC 781. UC 781 dissolution rate was markedly improved as compared to the physical mixtures and the pure drug, attaining maximum drug releases of up to 100% after only 5 min in the case of TPGS 1000-UC 781-PVPVA 64 solid dispersions and 30 min in TPGS 1000-UC 781-HPMC 2910. The increased UC 781 dissolution rate could be maintained when formulating UC 781 in PVPVA 64 tablets. The latter disintegrated in only 4 min, reaching drug releases of up to 90% (w/w). In addition, as opposed to the corresponding solid dispersions, no decrease in drug release occurred upon dissolution of PVPVA 64 tablets when the pH was increased to 6.8. Contrary to the PVPVA 64 tablet formulations, HPMC 2910 tablets showed a slow dissolution process due to the gelling nature of the polymer. The drug was slowly released as HPMC 2910 dissolved in the medium, however also in this case 90% (w/w) of the drug was dissolved after 4 h. Both polymers formed compatible blends in combination with the drug. Thermal analysis of the ternary mixtures revealed eutectic behavior exhibiting an extremely fine dispersion of the drug in the carrier. This was confirmed by the fact that no drug crystals could be detected using X-ray diffraction (XRD). As opposed to the physical mixtures, PVPVA 64 and HPMC 2910 solid dispersions did not contain any isolated polymer-rich phases, hence showed improved homogeneity. Amorphous TPGS 1000 clusters occurred in PVPVA 64 and HPMC 2910 formulations upon addition of at least 10% (w/w) UC 781, showing extremely low glass transition temperatures depending of the thermal history of the samples.
Goddeeris
Caroline
C
Laboratory of Pharmacotechnology and Biopharmacy, Catholic University of Leuven, O&N2, 9/921, Herestraat 49, B-3000 Leuven, Belgium.
Willems
Tom
T
Van den Mooter
Guy
G
D000813:Anilides / Q000737:chemistry*; D019380:Anti-HIV Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D005663:Furans / Q000737:chemistry*; D065347:Hypromellose Derivatives; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008956:Models, Chemical; D011092:Polyethylene Glycols / Q000737:chemistry; D011205:Povidone / Q000031:analogs & derivatives* / Q000737:chemistry; D011759:Pyrrolidines; D012995:Solubility; D013607:Tablets; D013678:Technology, Pharmaceutical; D013816:Thermodynamics; D013854:Thioamides; D044366:Transition Temperature; D014753:Vinyl Compounds; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry
D000813:Anilides; D019380:Anti-HIV Agents; D004337:Drug Carriers; D005663:Furans; D011759:Pyrrolidines; D013607:Tablets; D013854:Thioamides; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D014810:Vitamin E; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D008747:Methylcellulose; D011205:Povidone; C100668:UC-781; C014225:tocophersolan