Gastric retentive oral dosage form with restricted drug release in the lower gastrointestinal tract

Abstract

Controlled release oral dosage forms are provided for the continuous, sustained administration of a pharmacologically active agent to the upper gastrointestinal tract of a patient in whom the fed mode as been induced. The majority of the agent is delivered, on an extended release basis, to the stomach, duodenum and upper regions of the small intestine, with drug delivery in the lower gastrointestinal tract and colon substantially restricted. The dosage form comprises a matrix of a biocompatible, hydrophilic, erodible polymer with an active agent incorporated therein, wherein the polymer is one that both swells in the presence of water and gradually erodes over a time period of hours, with swelling and erosion commencing upon contact with gastric fluid, and drug release rate primarily controlled by erosion rate.

1 . A dosage form comprising:
 a polymer matrix and a neuroleptic agent dispersed in said polymer matrix, said polymer matrix comprised of a polymer wherein the polymer matrix:   (a) upon imbibition of water swells to a size effective to promote gastric retention for a time period of about 2 to 12 hours, and   (b) maintains the size for the time period before the polymer matrix is diminished by erosion,   wherein at least 75 wt % of the neuroleptic agent is released by erosion of the polymer matrix within the time period.   
     
     
         2 . The dosage form of  claim 1 , wherein the dosage form is a bilayer or trilayer tablet. 
     
     
         3 . The dosage form of  claim 1 , wherein the neuroleptic agent is selected from the group consisting of an antidepressant, an antimanic and an antipsychotic drug. 
     
     
         4 . The dosage form of  claim 1 , wherein the neuroleptic agent is quetiapine or a pharmaceutically acceptable salt thereof. 
     
     
         5 . The dosage form of  claim 1 , wherein at least 40 wt % of the neuroleptic agent is released within 4 hours. 
     
     
         6 . The dosage form of  claim 1 , wherein at least 80 wt % of the neuroleptic agent is released within the time period. 
     
     
         7 . The dosage form of  claim 1 , wherein the dosage form comprises a therapeutically effective amount of the neuroleptic agent. 
     
     
         8 . The dosage form of  claim 1 , wherein the neuroleptic agent in the dosage form is present in a range of about 0.01% to 80% of the dosage form by volume. 
     
     
         9 . The dosage form of  claim 1 , characterized by an erosion rate (ER) to dissolution rate (DR) ratio of approximately 1.1:1 to 5:1, wherein ER is the rate of the neuroleptic agent release in an aqueous medium measured using an in vitro disintegration test, and DR is the rate of the neuroleptic agent release in an aqueous medium measured using an in vitro dissolution test. 
     
     
         10 . The dosage form of  claim 1 , wherein the dosage form characterized by an ER to DR ratio of approximately 1.2:1 to approximately 3:1. 
     
     
         11 . The dosage form of  claim 1 , wherein the dosage form is characterized by an ER to DR ratio of approximately 1.3:1 to approximately 2:1. 
     
     
         12 . The dosage form of  claim 1 , wherein the dosage form is characterized by an ER to DR ratio of approximately 1.5:1 to approximately 2:1. 
     
     
         13 . The dosage form of  claim 1 , wherein the dosage form comprises a second active agent. 
     
     
         14 . A dosage form comprising:
 a polymer matrix and quetiapine or pharmaceutically acceptable salt thereof dispersed in the polymer matrix, the polymer matrix comprised of a hydrophilic polymer, wherein the polymer matrix:   (a) upon imbibition of water swells unrestrained dimensionally to a size effective to promote gastric retention for a time period of about 2 to 12 hours, and   (b) maintains the size for the time period before the size is diminished by erosion,   wherein at least 75 wt % of the quetiapine in the dosage form is released by erosion of the polymer matrix within the time period.   
     
     
         15 . The dosage form of  claim 14 , wherein greater than 90 wt % or 95 wt % of the quetiapine is released within about 8 hours. 
     
     
         16 . The dosage form of  claim 14 , wherein greater than 90 wt % or 95 wt % of the quetiapine is released within about 6 hours. 
     
     
         17 . A dosage form comprising:
 a first layer comprising a polymer matrix and a second layer comprising a neuroleptic agent or pharmaceutically acceptable salt thereof,   wherein the first layer:   (a) upon imbibition of water swells to a size effective to promote gastric retention of the dosage form for a time period of about 2 to 12 hours, and   (b) maintains the size for the time period before the size is diminished by erosion.   wherein at least 75 wt % of the neuroleptic agent in the dosage form is released from the dosage form within the time period.   
     
     
         18 . The dosage form of  claim 17 , wherein greater than 90 wt % or 95 wt % of the neuroleptic agent is released within about 8 hours.