#$%^&*AU2013204408A120130509.pdf#####DRUG DELIVERY SYSTEMS COMPRISING WEAKLY BASIC SELECTIVE SEROTONIN 5-HT3 BLOCKING AGENT AND ORGANIC ACIDS Abstract 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- HT 3 blocking agent having a pKa in the range of from about 5 to 14 and a solubility of not more than about 200 pg/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-HT 3 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. Figure 11/7 pH - solubility Profile of Ondansetron Hydrochloride Dihydrate 800700600E 400 00 200 100 0, 0 2 4 6 8 10 pH FIG. 1A pH - solubility Profile of Carvedilol 43.5. 32 2.5 21 0.5 00 1 2 3 4 5 6 7 8 pH FIG. 1B
