MULTIPHASIC PHARMACEUTICAL COMPOSITIONS OF BADLY SOLUBLE MEDICINAL COMPOUNDS IN WATER TO REDUCE VARIABILITY WHEN RECEIVING AFTER FOOD / NORTH AMERICA AND TO IMPROVE ORAL ORAL BIOAVAILABILITY

摘要

1. A pharmaceutical composition comprising a multiphase pharmaceutical composition in an oral dosage form in which:! (a) the composition exhibits less variability in the average AUC values, average Cmax and / or average Tmax values when the composition is administered to a mammal after eating compared to administering the pharmaceutical composition comparing the same active pharmaceutical ingredient on an empty stomach in the same dosage, the composition including:! (b) a composition that contains:! (i) an active pharmaceutical ingredient, wherein the active pharmaceutical ingredient is in particulate form, in dissolved form, or both in particulate form and in dissolved form; ! (ii) a solvent; ! (iii) immiscible liquid; ! (iv) a stabilizing substance; and! (v) water. ! 2. The pharmaceutical composition according to claim 1, the absorption profile of which, when administered to a mammal after a meal, is similar to or bioequivalent to the absorption profile of the same composition, administered on an empty stomach. ! 3. The pharmaceutical composition according to claim 2, in which the mammal is a human. ! 4. The pharmaceutical composition according to claim 1, in which when the composition is administered to rats or on a rat model, the difference between the average AUC determined after ingestion and the average AUC determined on an empty stomach is less than about 90,000 h × ng / ml ! 5. The pharmaceutical composition according to claim 4, in which the difference is selected from the group consisting of values less than approximately 85,000 h × ng / ml, less than approximately 80,000 h × ng / ml, less than approximately 75,000 h × ng / ml, less than approximately 70,000 h × ng / ml, less than approximately 65,000 h × ng / ml, less than approximately