Ondansetron Orally Disintegrating Tablet Compositions for Prevention of Nausea and Vomiting
First Claim
1. An ODT comprising:
- at least one population of taste-masked immediate-release (IR) drug microparticles comprising a selective serotonin 5-HT3 blocking agent, wherein the taste-masked IR microparticles provide dissolution profiles similar to that of a reference drug product;
at least one population of timed, pulsatile release (TPR) beads comprising the selective serotonin 5-HT3 blocking agent and at least one pharmaceutically acceptable organic acid, wherein the organic acid is not depleted from the TPR beads until completion of the drug release from the dosage form when dissolution tested by United States Pharmacopoeia (USP) dissolution methodology (Apparatus 2—
paddles@ 50 RPM and a two-stage dissolution medium at 37°
C. (first 2 hours in 0.1N HCl followed by testing in a buffer at pH 6.8); and
rapidly dispersing microgranules comprising at least one super disintegrant and at least one sugar alcohol, a saccharide, or a mixture thereof
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Accused Products
Abstract
This invention is related to a pharmaceutical composition in the patient-friendly orally disintegrating tablet form comprising a weakly basic, selective serotonin 5-HT3 blocking agent for the prevention of nausea and/or vomiting for up to 24 hrs postdosing in cancer patients prior to undergoing moderately emetogenic chemotherapy or partial or whole body radiotherapy or in subjects at moderate to high risk of postoperative or postdischarge nausea and/or vomiting prior to inpatient or outpatient ambulatory surgery. The unit dosage form comprising a multitude of immediate-release drug particles providing dissolution profiles similar to that of reference drug product, and one or more timed, pulsatile-release bead populations, comprising 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, is capable of delivering said antiemetic agent in patients in need thereof in a sustained-released fashion to be suitable for a once-daily dosing regimen.
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Citations
36 Claims
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1. An ODT comprising:
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at least one population of taste-masked immediate-release (IR) drug microparticles comprising a selective serotonin 5-HT3 blocking agent, wherein the taste-masked IR microparticles provide dissolution profiles similar to that of a reference drug product; at least one population of timed, pulsatile release (TPR) beads comprising the selective serotonin 5-HT3 blocking agent and at least one pharmaceutically acceptable organic acid, wherein the organic acid is not depleted from the TPR beads until completion of the drug release from the dosage form when dissolution tested by United States Pharmacopoeia (USP) dissolution methodology (Apparatus 2—
paddles@ 50 RPM and a two-stage dissolution medium at 37°
C. (first 2 hours in 0.1N HCl followed by testing in a buffer at pH 6.8); andrapidly dispersing microgranules comprising at least one super disintegrant and at least one sugar alcohol, a saccharide, or a mixture thereof - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 33, 34, 35)
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29. A method for the preparation of a multiparticulate ODT tablet comprising a selective serotonin 5-HT3 blocking agent, and at least one pharmaceutically acceptable organic acid, comprising the steps of:
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preparing rapidly releasing selective serotonin 5-HT3 blocking agent-containing immediate release (IR) microparticles; applying a taste-masking membrane comprising a water-insoluble polymer or a water-insoluble polymer in combination with a gastrosoluble pore-forming agent, over the IR microparticles; preparing organic acid cores; coating the organic acid cores with an SR or TPR coating comprising a water-insoluble polymer alone or a water-insoluble polymer in combination with a water-soluble polymer or an enteric polymer at a ratio of from about 95;
5 to about 50;
50 for a coating weight of up to about 30%, to provide a sustained-release profile;layering the selective serotonin 5-HT3 blocking agent or pharmaceutically acceptable salt thereof from a polymer binder solution onto the SR- or TPR-coated organic acid cores and optionally applying a protective seal-coat with a water-soluble polymer; optionally applying a barrier (SR) coating of a water-insoluble polymer, or a water-insoluble polymer in combination with a water-soluble polymer at a ratio of from about 95;
5 to about 50;
50 to the selective serotonin 5-HT3 blocking agent layered beads for a weight gain of from about 1.5% to 20% by dry weight of the coated IR beads;applying an outer lag-time coating to the selective serotonin 5-HT3 blocking agent layered beads, wherein the outer lag-time coating comprises a water-insoluble polymer in combination with an enteric polymer at a ratio of from about 9;
1 to 1;
3 for a weight gain of from about 10% to 60% by weight of the coated bead; andpreparing rapidly dispersing microgranules comprising a super disintegrant, at least one sugar alcohol, a saccharide, or a mixture thereof, each primary particle having an average particle size of not more than 30 μ
m by high shear granulation and fluid bed drying or tray drying;blending/compressing appropriate amounts of each of rapidly dispersing microgranules, taste-masked IR microparticles, TPR beads, and other pharmaceutically acceptable excipients, into ODT tablets. - View Dependent Claims (30, 31, 32, 36)
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Specification