| Title | Inulin solid dispersion technology to improve the absorption of the BCS Class IV drug TMC240. | | Author(s) | Visser MR, Baert L, van 't Klooster G, Schueller L, Geldof M, Vanwelkenhuysen I, De Kock H, De Meyer S, Frijlink HW, Rosier J, Hinrichs WL | | Institution | Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. | | Source | Eur J Pharm Biopharm 2009 Oct 24. | | Abstract | TMC240 is a very poorly soluble and poorly permeating HIV protease inhibitor. In order to enhance its oral bioavailability, a fast dissolving inulin based solid dispersion tablet was developed. During the dissolution test in water (0.5 or 1.0% SLS), this tablet released at least 80% of TMC240 within 30 min, while the physical mixture tablet of the same composition released only 6% after 2 h. In a subsequent single-dose study in dogs (200 mg of TMC240), plasma concentrations of TMC240 remained below the lower limit of quantification (<1.00 ng/mL) in all animals (n=3 per tested formulation), except in one dog receiving the inulin solid dispersion tablet (C(max)=1.8 ng/mL, AUC(0-7h)=3.0 ng.h/mL). In the latter treatment group, ritonavir co-administration (10 mg/kg b.i.d.) increased TMC240 exposure more than 30-fold (mean AUC(0-7h)=108 ng.h/mL; F(rel)=3588%). Exposure was also 16-fold higher than after TMC240 administration as PEG400 suspension in presence of ritonavir (AUC(0-7h)=6.7 ng.h/mL). The current data demonstrate that a solid dispersion of TMC240 in an inulin matrix allows considerable improvement in the release of poorly water-soluble TMC240, both in vitro in presence of a surfactant and in vivo upon oral administration. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19861163 |
|
