Bimodal release ondansetron tablets and methods of treating nausea and vomiting

Abstract

A solid oral dosage form includes a core comprising a non-ionic polymer matrix, a first amount of a first antiemetic drug or a pharmaceutically acceptable salt thereof dispersed within the matrix, and a salt dispersed within the matrix; a first seal coat of a non-ionic polymer matrix surrounding the core; and an immediate release drug layer surrounding the first seal coat, wherein the immediate release drug layer comprises a non-ionic polymer and a second amount of a second antiemetic drug or a pharmaceutically acceptable salt thereof dispersed therein, wherein the drug layer is sufficiently designed to release the second amount of the antiemetic drug over a period of at least 1 hour, wherein the solid oral dosage form is sufficiently designed to release the first amount of the first antiemetic drug and the second amount of the second antiemetic drug over a minimum period of 16 hours.

What is claimed is: 
     
         1 . A bimodal release ondansetron tablet comprising:
 an internal portion comprising a hydrophilic swellable matrix, in which is disposed a first amount of ondansetron or an equivalent amount of an ondansetron salt thereof and one or more electrolytes selected from one or two members of the group consisting of sodium chloride, sodium bicarbonate, potassium bicarbonate, sodium citrate, sodium bisulfate, sodium sulfite, magnesium sulfate, calcium chloride, potassium chloride, and sodium carbonate;   a first seal coat surrounding the internal portion, wherein the first seal coat comprises hypromellose and wherein the first seal coat does not substantially affect the release of the ondansetron from the tablet;   an immediate release drug layer overcoat surrounding the first seal coat and comprising a second amount of ondansetron or an equivalent amount of an ondansetron salt thereof; and   a second seal coat surrounding the immediate release drug layer, wherein the second seal coat comprises hypromellose and wherein the second seal coat does not substantially affect the release of the ondansetron from the tablet.   
     
     
         2 . The bimodal release ondansetron tablet of  claim 1 , further comprising an enteric coating surrounding the first seal coat. 
     
     
         3 . The bimodal release ondansetron tablet of  claim 1 , wherein the first and second seal coat further comprises a coating additive. 
     
     
         4 . The bimodal release ondansetron tablet of  claim 3 , wherein the coating additive is an aqueous emulsion of glyceryl monostearate and triethyl citrate. 
     
     
         5 . The bimodal release ondansetron tablet of  claim 1 , wherein one of the one or more electrolytes is sodium citrate. 
     
     
         6 . The bimodal release ondansetron tablet of  claim 5 , wherein the sodium citrate is sodium dihydrogen citrate anhydrous present at a concentration in the range of 50% to 100% by weight of the hydrophilic swellable matrix. 
     
     
         7 . The bimodal release ondansetron tablet of  claim 1 , wherein up to 75% of the total dosage form weight is included in the internal portion. 
     
     
         8 . The bimodal release ondansetron tablet of  claim 1 , wherein the drug layer overcoat yields a burst of 25% ondansetron. 
     
     
         9 . The bimodal release ondansetron tablet of  claim 1 , wherein the second amount of ondansetron is ⅓ the first amount of ondansetron. 
     
     
         10 . The bimodal release ondansetron tablet of  claim 1 , wherein the internal portion comprises the equivalent of 18 mg of ondansetron and the immediate release layer comprises the equivalent of 6 mg of ondansetron. 
     
     
         11 . A method of treating nausea in a patient comprising administering the bimodal release ondansetron tablet of  claim 1 . 
     
     
         12 . The method of  claim 11 , wherein the bimodal release ondansetron tablet is administered once daily. 
     
     
         13 . A method of treating vomiting in a patient comprising administering the bimodal release ondansetron tablet of  claim 1 . 
     
     
         14 . The method of  claim 13 , wherein the bimodal release ondansetron tablet is administered once daily. 
     
     
         15 . A packaged pharmaceutical preparation comprising a plurality of the bimodal release ondansetron tablets of  claim 1  in a sealed container and instructions for administering the tablets orally to a patient to treat nausea. 
     
     
         16 . A packaged pharmaceutical preparation comprising a plurality of the bimodal release ondansetron tablets of  claim 1  in a sealed container and instructions for administering the tablets orally to a patient to treat vomiting.