| 主权项 |
1. A pharmaceutical composition comprising from about 0.5 to about 7 mg of doxepin, or a pharmaceutically acceptable salt thereof, and from about 92% to about 99.8% w/w silicified microcrystalline cellulose, the composition having one or more of the characteristics selected from the group consisting of: a hardness value of at least 2 Kp, a friability value of 1% or less, a disintegration time of about 1 minute as per USP protocols, at least an 80% release of doxepin within 15 minutes using compendial method for measuring dissolution of doxepin, at least an 85 percent release of doxepin within 30 minutes using U.S. Pharmacopeia (USP) Apparatus I at 100 rpm (or Apparatus II at 50 rpm) in 0.1 N HCl or Simulated Gastric Fluid USP without enzymes, at least an 85 percent release of doxepin within 30 minutes using U.S. Pharmacopeia (USP) Apparatus I at 100 rpm (or Apparatus II at 50 rpm) in a pH 4.5 buffer, and at least an 85 percent release of doxepin within 30 minutes using U.S. Pharmacopeia (USP) Apparatus I at 100 rpm (or Apparatus II at 50 rpm) in a pH 6.8 buffer or Simulated Intestinal Fluid USP without enzymes; and
wherein the pharmaceutical composition has dissolution and bioavailablity characteristics such that after administration to a 70 kg human, the composition provides a plasma concentration of at least 0.05 ng/mL doxepin within a time frame of not more than about 90 minutes. |
