Pharmaceutical compositions comprising ibuprofen and domperidone

Abstract

A stable pharmaceutical composition comprising a mixture of (i) an ibuprofen medicament; (ii) a domperidone medicamement; and (iii) a carrier material characterized in that the carrier material is substantially free of povidone and comprises at least one diluent combined with at least one release modifying agent.

1 .- 24 . (canceled)  
   
   
       25 . A process for preparing a stable pharmaceutical composition comprising a mixture of 
 (i) an ibuprofen medicament;    (ii) 0.1 to 20% by weight of a domperidone medicament based on the total weight of the composition; and    (iii) a carrier material    characterised in that the carrier material is substantially free of povidone and comprises at least one diluent combined with at least one disintegrating agent, excluding    (a) a compressed tablet comprising granulated ibuprofen and a carrier material consisting essentially of either maize starch at 35-38% total tablet weight in combination with dried maize starch at 3-4% total tablet weight or microcrystalline cellulose at 10-11% total tablet weight in combination with croscarmellose sodium at 14-16% total tablet weight and pre-gelled starch at 10% total tablet weight;    (b) a direct compression tablet comprising a carrier material consisting essentially of microcrystalline cellulose at 8-11% total tablet weight and lactose at 5-6% total tablet weight;    (c) a hard gelatin capsule comprising a carrier consisting essentially of maize starch at 15-20% total capsule contents weight in combination with pre-gelled starch at 5-6% total capsule contents weight;    wherein the process comprises combining said ibuprofen medicament and said domperidone medicament with said carrier material to form a homogeneous blend and forming said homogeneous blend into a unit dosage form.    
   
   
       26 . A process as claimed in  claim 25  wherein said homogeneous blend is compressed to form a tablet.  
   
   
       27 . A process as claimed in  claim 25  wherein said homogeneous blend is directly compressed to form a tablet.  
   
   
       28 . A process as claimed in  claim 25  wherein the carrier material is present in an amount of 20-60% by weight based on the total weight of the pharmaceutical composition.  
   
   
       29 . A process as claimed in  claim 25  wherein the carrier material consists essentially of one or more of the following diluents: microcrystalline cellulose, tricalcium phosphate and lactose.  
   
   
       30 . A process as claimed in  claim 25  wherein said ibuprofen medicament is racemic ibuprofen or S-(+)-ibuprofen or the sodium or lysine salts thereof, present to an extent of 50 to 65% by weight of the pharmaceutical composition, and said domperidone medicament is domperidone or the maleate salt thereof, present to an extent of 1 to 5% by weight of the pharmaceutical composition.  
   
   
       31 . A process as claimed in  claim 25  wherein the carrier material includes one or more discrete disintegrants.  
   
   
       32 . A process as claimed in  claim 25  wherein said ibuprofen medicament is granulated with at least a first portion of said carrier material to form a granular composition; blending the granular composition with a lubricating agent, said domperidone medicament and optionally a flow aid to form said homogeneous blend, and compressing the homogeneous blend to form a tablet.  
   
   
       33 . A process as claimed in  claim 32  wherein the carrier material is present in an amount of 20-60% by weight based on the total weight of the pharmaceutical composition.  
   
   
       34 . A process as claimed in  claim 32  wherein the carrier material consists essentially of one or more of the following diluents: microcrystalline cellulose, tricalcium phosphate and lactose.  
   
   
       35 . A process as claimed in  claim 32  wherein said ibuprofen medicament is racemic ibuprofen or S-(+)-ibuprofen or the sodium or lysine salts thereof, present to an extent of 50 to 65% by weight of the pharmaceutical composition, and said domperidone medicament is domperidone or the maleate salt thereof, present to an extent of 1 to 5% by weight of the pharmaceutical composition.  
   
   
       36 . A process as claimed in  claim 32  wherein the carrier material includes one or more discrete disintegrants.  
   
   
       37 . A process as claimed in  claim 25  wherein said ibuprofen medicament is granulated with said domperidone medicament and at least a first portion of said carrier material to form a granular composition, blending the granular composition with a lubricating agent and optionally a flow aid to form said homogeneous blend, and compressing the homogeneous blend to form a tablet.  
   
   
       38 . A process as claimed in  claim 37  wherein the carrier material is present in an amount of 20-60% by weight based on the total weight of the pharmaceutical composition.  
   
   
       39 . A process as claimed in  claim 37  herein the carrier material consists essentially of one or more of the following diluents: microcrystalline cellulose, tricalcium phosphate and lactose.  
   
   
       40 . A process as claimed in  claim 37  wherein said ibuprofen medicament is racemic ibuprofen or S-(+)-ibuprofen or the sodium or lysine salts thereof, present to an extent of 50 to 65% by weight of the pharmaceutical composition, and said domperidone medicament is domperidone or the maleate salt thereof, present to an extent of 1 to 5% by weight of the pharmaceutical composition.  
   
   
       41 . A process as claimed in  claim 37  wherein the carrier material includes one or more discrete disintegrants.  
   
   
       42 . A process as claimed in  claim 25  wherein said ibuprofen medicament is granulated with at least a first portion of said carrier material and a granulating fluid to form a granular composition, drying said granular composition, blending the dried granular composition with a lubricating agent, said domperidone medicament and optionally a flow aid to form said homogeneous blend, and compressing the homogeneous blend to form a tablet.  
   
   
       43 . A process as claimed in  claim 42  wherein said granular composition is formed in the presence of a granulating agent.  
   
   
       44 . A process as claimed in  claim 43  wherein said granulating agent is present in an amount of up to 10% by weight based on the total weight of the tablet.  
   
   
       45 . A process as claimed in  claim 43  wherein said granulating agent consists essentially of one or more of the following: 
 a polymeric granulating agent selected from the group consisting of natural gums, synthetic gums and cellulose materials; a sugar granulating agent; a starch granulating agent.    
   
   
       46 . A process as claimed in  claim 45  wherein the granulating agent is a cellulose derivative.  
   
   
       47 . A process as claimed in  claim 42  wherein the granulating fluid is selected from the group consisting of water or a C1-C6 alkanol and combinations thereof.  
   
   
       48 . A process as claimed in  claim 42  wherein the carrier material is present in an amount of 20-60% by weight based on the total weight of the pharmaceutical composition.  
   
   
       49 . A process as claimed in  claim 42  wherein the carrier material consists essentially of one or more of the following diluents: microcrystalline cellulose, tricalcium phosphate and lactose.  
   
   
       50 . A process as claimed in  claim 42  wherein said ibuprofen medicament is racemic ibuprofen or S-(+)-ibuprofen or the sodium or lysine salts thereof, present to an extent of 50 to 65% by weight of the pharmaceutical composition, and said domperidone medicament is domperidone or the maleate salt thereof, present to an extent of 1 to 5% by weight of the pharmaceutical composition.  
   
   
       51 . A process as claimed in  claim 42  wherein the carrier material includes one or more discrete disintegrants.  
   
   
       52 . A composition comprising a mixture of 
 (i) an ibuprofen medicament;    (ii) 0.1 to 20% by weight of a domperidone medicament based on the total weight of the composition; and    (iii) a carrier material    in the form of a compressed tablet wherein the carrier material comprises a compressed mixture of:    (a) a granular component comprising said ibuprofen medicament at least a first portion of said carrier material; and    (b) a powder component comprising a lubricant material and an optional further portion of said carrier material,    said domperidone medicament being present in either of components (a) and (b), characterised in that the carrier material is subtantially free of povidone and comprises at least one diluent combined with at least one disintegrating agent, but excluding    (a) a compressed tablet comprising granulated ibuprofen and a carrier material consisting essentially of either maize starch at 35-38% total tablet weight in combination with dried maize starch at 3-4% total tablet weight or microcrystalline cellulose at 10-11% total tablet weight in combination with croscarmellose sodium at 14-16% total tablet weight and pre-gelled starch at 10% total tablet weight;    (b) a direct compression tablet comprising a carrier material consisting essentially of microcrystalline cellulose at 8-11% total tablet weight and lactose at 5-6% total tablet weight;    (c) a hard gelatin capsule comprising a carrier consisting essentially of maize starch at 15-20% total capsule contents weight in combination with pre-gelled starch at 5-6% total capsule contents weight.