Antiemetic extended release solid dosage forms

Abstract

A pharmaceutical formulation includes (1) a first dosage component 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 an electrolyte dispersed within the matrix; a first seal coat surrounding the core, the first seal coat comprising 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; and (2) a second dosage component comprising: a core comprising a third amount of ondansetron or an equivalent amount of an ondansetron salt thereof, at least one filler, and a lubricant; and a coating surrounding the core, the coating comprising water and a mixture of methacrylic acid-alkyl acrylate copolymers with alkaline groups.

What is claimed is: 
     
         1 . A pharmaceutical formulation comprising:
 (1) a first dosage component comprising:
 a core comprising a non-ionic polymer matrix providing sustained release, a first amount of ondansetron or an equivalent amount of an ondansetron salt thereof dispersed within the matrix, and an electrolyte dispersed within the matrix; 
 a first seal coat surrounding the core, the first seal coat comprising 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; and 
   (2) a second dosage component comprising:
 a core comprising a third amount of ondansetron or an equivalent amount of an ondansetron salt thereof, at least one filler, and a lubricant; and 
 a coating surrounding the core, the coating comprising water and a mixture of methacrylic acid-alkyl acrylate copolymers with alkaline groups. 
   
     
     
         2 . The pharmaceutical formulation of  claim 1  wherein the core of the first dosage component is a compressed core. 
     
     
         3 . The pharmaceutical formulation of  claim 1  wherein the core of the second dosage component is a compressed core. 
     
     
         4 . The pharmaceutical formulation of  claim 1  wherein the coating of the second dosage component includes a mixture of Eudragit® RS to Eudragit® RL, 
     
     
         5 . The pharmaceutical formulation of  claim 4  wherein a Eudragit® RS/Eudragit® RL ratio is 8 to 2. 
     
     
         6 . The pharmaceutical formulation of  claim 1  wherein the coating of the second dosage component further includes talc. 
     
     
         7 . The pharmaceutical formulation of  claim 1  wherein the coating of the second dosage component comprises:
 from about 30% (w/w) to about 55% (w/w) of purified water; 
 from about 25% (w/w) to about 45% (w/w) of Eudragit® RS 30D; 
 from about 3.0% (w/w) to about 25% (w/w) of Eudragit® RL 30D; and 
 from about 1.0% (w/w) to about 6.0% (w/w) of talc. 
 
     
     
         8 . The pharmaceutical formulation of  claim 1  wherein the first component and the second component are compressed together. 
     
     
         9 . The pharmaceutical formulation of  claim 1  wherein the first component and the second component are two separate units. 
     
     
         10 . The pharmaceutical formulation of  claim 1  wherein the first amount of ondansetron is about 20 mg of active free base. 
     
     
         11 . The pharmaceutical formulation of  claim 1  wherein the first amount of ondansetron is about 28 mg of active free base. 
     
     
         12 . The pharmaceutical formulation of  claim 1  wherein the second amount of ondansetron is about 8 mg of active free base. 
     
     
         13 . The pharmaceutical formulation of  claim 1  wherein the third amount of ondansetron is about 8 mg of active free base. 
     
     
         14 . A packaged pharmaceutical preparation comprising a plurality of the pharmaceutical formulations of  claim 1  in a sealed container and instructions for administering the pharmaceutical formulations orally to effect prevention of nausea and vomiting. 
     
     
         15 . A packaged pharmaceutical preparation comprising a plurality of the pharmaceutical formulations of  claim 1  each in a discrete sealed housing, and instructions for administering the pharmaceutical formulations orally to effect prevention of nausea and vomiting. 
     
     
         16 . A method for preventing nausea and vomiting comprising the step of administering the pharmaceutical formulation of  claim 1  to a patient. 
     
     
         17 . The pharmaceutical formulation of  claim 1  wherein the single oral dosage form is sufficiently designed to release all of the ondansetron over a minimum period of 36 hours. 
     
     
         18 . The pharmaceutical formulation of  claim 1  wherein the single oral dosage form is sufficiently designed to release all of the ondansetron over a minimum period of 40 hours. 
     
     
         19 . The pharmaceutical formulation of  claim 1  wherein the single oral dosage form is sufficiently designed to release all of the ondansetron over a minimum period of 44 hours. 
     
     
         20 . The pharmaceutical formulation of  claim 1  wherein the single oral dosage form is sufficiently designed to release all of the ondansetron over a minimum period of 48 hours. 
     
     
         21 . The pharmaceutical formulation of  claim 1  sufficiently designed to meet the two stage test dissolution profile in a basket apparatus:
 (a) release of not more than 25% of the total amount of ondansetron in 2 hours in an acid stage comprising 900 ml 0.1N HCl at 50 rpm; and 
 (b) release of not less than 40% of the total amount of ondansetron in 30 hours in 900 ml phosphate buffer pH 6.8 at 50 rpm following the acid stage.