Patent ID: 7108866

Claim:
An orally administrable controlled-release composition comprising a pharmaceutically acceptable form of diltiazem selected from the group consisting of diltiazem and the pharmaceutically acceptable salts thereof, suitable for evening dosing every 24 hours, the dosage comprising at least one bead comprising a core and at least one coating, the at least one bead being formulated in an oral dosage form containing from about 120 mg to about 540 mg of the form of diltiazem, the diltiazem in the core of each bead associated with excipients, the at least one coating covering the core comprising an amount of a water swellable and diffusible coating which permits hydration of the core by gastrointestinal fluids, the water swellable and diffusible coating comprising the following constituents: (i) an amount of at least one hydrophilic polymer which is selected from the group consisting of hydroxypropylmethylcellulose, hydroxyethylcellulose, and hydroxypropylcellulose, and/or an amount of at least one lubricant which is selected from the group consisting of talc, and magnesium stearate; and (ii) an amount at least one water-, acid- or base-insoluble neutral acrylic polymer, wherein said constituents (i) and (ii) which comprise said coating, the ratios thereof, and the amount of said coating are formulated such that said orally administrable composition: A) in vitro exhibits the following in vitro release characteristics; (i) releases the diltiazem or a pharmaceutically acceptable salt thereof into an aqueous medium at the following rates when measured using the method of United States Pharmacopoeia No. XXIII at 100 rpm in 900 ml of water: (a) between about 1% and about 15% after about 2 hours; (b) between about 7% and about 35% after about 4 hours; (c) between about 30% and about 58% after about 8 hours; (d) between about 55% and about 80% after about 14 hours; (e) in excess of about 75% after about 24 hours; and/or (ii) releases the diltiazem or pharmaceutically acceptable salt thereof into a buffered medium having a pH between about 5.5 and about 6.5, at the following rates measured using the method of United States Pharmacopoeia No. XXIII at 100 rpm in 900 ml of the buffered medium: (a) between about 1% and about 25% after about 2 hours; (b) between about 7% and about 45% after about 4 hours; (c) between about 30% and about 68% after about 8 hours; (d) in excess of about 75% after about 24 hours; and further wherein said orally administrable composition having said in vitro release characteristics results in a composition that: B) when orally given to humans exhibit the following properties: (i) a higher bioavailability when given at night compared to when given in the morning without food according to FDA guidelines or criteria and (ii) bioequivalence when given in the morning with or without food according to the same FDA guidelines or criteria; and (iii) provides a Cmax of diltiazem in the blood at between about 10 hours and 15 hours after administration.