DRUG DELIVERY SYSTEMS COMPRISING WEAKLY BASIC SELECTIVE SEROTONIN 5-HT3 BLOCKING AGENT AND ORGANIC ACIDS

摘要

A pharmaceutical dosage form such as a capsule, a conventional or orally disintegrating tablet capable of delivering a weakly basic, nitrogen (N)-containing selective serotonin 5- HT₃ blocking agent having a pKa in the range of from about 5 to 14 and a solubility of not more than about 200 µg/mL at pH 6.8 into the body in a sustained-released fashion, suitable for a once-daily dosing regimen, comprises at least one organic acid, which solubilizes said weakly basic selective serotonin 5-HT₃ blocking agent prior to releasing it into the hostile intestinal environment wherein the blocking agent is practically insoluble. The unit dosage form may be composed of a multitude of multicoated particulates (i.e., immediate-release beads, sustained-release beads and/or one or more timed, pulsatile- release bead populations) and is designed in such a way that the weakly basic blocking agent and the organic acid do not come into close contact during processing and/or storage thereby avoiding in-situ formation of acid addition compounds while ensuring that the acid is not depleted prior to completion of the drug release.