Timed, pulsatile release systems

摘要

A unit multiparticulate dosage form for delivering one or more basic, active pharmaceutical ingredients into the body in need of such medications to achieve target PK (pharmacokinetics) profiles is described. The dosage form comprises one or more multicoated drug particles (beads, pellets, mini-/micro-tablets) having a barrier coating and a lag-time coating. Each Timed Pulsatile Release (TPR) bead population exhibits pre-determined lag-time followed by differing release characteristics. The composition and thickness of the barrier coating, composition and thickness of the lag-time coating, ratio of IR beads to one or more TPR bead populations and total dose may be varied depending on the alkalinity, pH-dependent solubility and elimination half-life of the active ingredients to achieve target PK profiles (suitable for a once or twice daily dosing regimen) in patients in need of such medications.

主权项

1. A pharmaceutical composition comprising one or more populations of timed, pulsatile release beads, wherein at least one population of timed, pulsatile release beads comprises:
a) a core particle comprising an acidic active pharmaceutical ingredient or a pharmaceutically acceptable salt thereof; b) an inner barrier coating comprising a water insoluble polymer in combination with a water-soluble/pore-forming polymer; and c) an outer lag-time coating comprising a water-insoluble polymer in combination with an enteric polymer wherein the at least one population of timed, pulsatile release beads provides a lag time greater than 6 hours before onset of drug release when tested using USP Apparatus 1 or 2 and a two-stage dissolution medium (first two hours in 700 mL of 0.1N HCl and thereafter in 900 mL at pH 6.8).