Effects of Altered Formulation on the Bioequivalence of Tacrolimus in Healthy Female and Male Volunteeers

Amorphous solid dispersion (ASD) formulations are increasingly used by the pharmaceutical industry to develop poorly water-soluble drugs into effective oral dosage forms. Examples include the antifungal drug itraconazole, the HIV protease inhibitor combination, lopinavir/ritonavir and the immunosuppressive, tacrolimus. There is potential for significant variation in bioavailability of ASD and thus heightened concern regarding the therapeutic efficacy as generic versions of these poorly water-soluble compounds become approved. The variation in bioavailability is to be expected because of our limited understanding of the precise physical chemistry of drug polymer amorphous solid dispersion formulations.