Antiemetic extended release solid dosage forms

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 solid oral dosage form comprising:
 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 surrounding the core, wherein the first seal coat is comprised of a non-ionic polymer matrix; 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. 
     
     
         2 . The solid oral dosage form of  claim 1 , further comprising an enteric coating surrounding the first seal coat. 
     
     
         3 . The solid oral dosage form of  claim 1 , further comprising a second seal coat surrounding the immediate release drug layer, wherein the second seal coat is comprised of a non-ionic polymer. 
     
     
         4 . The solid oral dosage form of  claim 1 , in which upon exposure to an aqueous medium, the salt causes a hardened boundary around the periphery of the matrix, the boundary sequentially progressing inwardly toward the center thereof as the aqueous medium permeates the matrix, the hardened boundary limiting the rate at which the antiemetic drug in the matrix is released from the tablet. 
     
     
         5 . The solid oral dosage form of  claim 1 , wherein the first antiemetic drug and the second antiemetic drug are the same drug. 
     
     
         6 . The solid oral dosage form of  claim 1 , wherein the first antiemetic drug and the second antiemetic drug are different drugs. 
     
     
         7 . The solid oral dosage form of  claim 1 , wherein the first antiemetic drug and the second antiemetic drug are each ondansetron or an equivalent amount of an ondansetron salt thereof. 
     
     
         8 . A method for preventing nausea and vomiting comprising the step of administering a therapeutically-effective amount of the solid oral dosage form of  claim 1  to a patient. 
     
     
         9 . A solid oral dosage form comprising:
 a core comprising hypromellose, 18 mg of ondansetron or an equivalent amount of an ondansetron salt thereof, and sodium citrate anhydrous;   a first seal coat surrounding the core and comprising hypromellose; and   an immediate release drug layer surrounding the first seal coat and comprising hypromellose and 6 mg of ondansetron or an equivalent amount of an ondansetron salt thereof, the immediate release drug layer sufficient to release the ondansetron over a period of at least 1 hour,   
       wherein the total amount of ondansetron in the dosage form is released over 24 hours. 
     
     
         10 . The solid oral dosage form of  claim 9 , further comprising an enteric coating surrounding the first seal coat. 
     
     
         11 . The solid oral dosage form of  claim 9 , further comprising a second seal coat surrounding the immediate release drug layer, wherein the second seal coat is comprised of a non-ionic polymer. 
     
     
         12 . The solid oral dosage form of  claim 9 , in which upon exposure to an aqueous medium, the sodium citrate anhydrous causes a hardened boundary around the periphery of the hypromellose, the boundary sequentially progressing inwardly toward the center thereof as the aqueous medium permeates the hypromellose, the hardened boundary limiting the rate at which the ondansetron in the hypromellose is released from the tablet. 
     
     
         13 . The solid oral dosage form of  claim 9 , wherein, when the solid oral dosage form is administered to a patient in a fasting state, achieves a C max  of at least 40 ng/ml. 
     
     
         14 . The solid oral dosage form of  claim 9 , wherein, when the solid oral dosage form is administered to a patient in a fasting state, achieves AUC of at least 450 nghr/ml. 
     
     
         15 . The solid oral dosage form of  claim 9 , wherein a blood ondansetron concentration approximately 24 hours after oral administration of ondansetron (C min ) is at least 6 ng/ml. 
     
     
         16 . The solid oral dosage form of  claim 9 , wherein a ratio of a maximum blood ondansetron concentration (C max ) to a blood ondansetron concentration after approximately 24 hours from oral administration of ondansetron (C min ) is between 3 and 7. 
     
     
         17 . A solid oral dosage form comprising: a core comprising a non-ionic polymer matrix, a first amount of ondansetron or an equivalent amount of an ondansetron salt thereof dispersed within the matrix, and a salt dispersed within the matrix; a first seal coat surrounding the core, wherein the first seal coat is comprised of a non-ionic polymer matrix; 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 ondansetron or an equivalent amount of an ondansetron salt thereof dispersed therein, wherein the solid oral dosage form results in an in vitro ondansetron dissolution profile when measured in a type 2 paddle dissolution apparatus at 37° C. in aqueous solution containing distilled water at 50 rpm that exhibits: a) from about 20% to 50% of the total ondansetron is released after two and a half hours of measurement in the apparatus; b) from about 50% to 70% of the total ondansetron is released after five hours of measurement in the apparatus; and c) no less than about 90% of the total ondansetron is released after fifteen hours of measurement in the apparatus. 
     
     
         18 . The solid oral dosage form of  claim 17 , wherein, when the solid oral dosage form is administered to a patient in a fasting state at a dose of 24 mg ondansetron, achieves a C max  of at least 40 ng/ml. 
     
     
         19 . The solid oral dosage form of  claim 17 , wherein, when the solid oral dosage form is administered to a patient in a fasting state at to dose of 24 mg ondansetron, achieves AUC of at least 450 nghr/ml. 
     
     
         20 . A method for preventing nausea and vomiting comprising the step of administering a therapeutically-effective amount of the solid oral dosage form of  claim 17  to a patient.