Formulations

Abstract

The present invention relates to pharmaceutical compositions for oral administration of active compounds.

1 . Oral pharmaceutical composition containing at least two separate formulations: 
 a first formulation, which contains an active compound selected from 2-[4-(diphenylmethyl)-1-piperazinyl]-acetic acids and their amides having the general formula I                          wherein    R 1  is a —COOH group or a —CONH 2  group, and    X 1  and X 2 , taken separately, each represent a hydrogen atom, a halogen atom, a straight-chain or branched C 1 -C 4  alkoxy group or a trifluoromethyl group as well as their pharmaceutically acceptable salts, geometrical isomers, enantiomers, diastereomers and mixtures thereof, and which first formulation does not contain polyols having a molecular weight of less than 300 in a molar ratio between the polyol and active compound of formula I above 10; and 
 a second formulation, which contains one or more solid polyol(s) with a molecular weight of less than 3000 and is free of any drug.  
   
     
     
         2 . A composition according to  claim 1  wherein the first formulation does not contain polyols having a molecular weight of less than 950 in a molar ratio between polyol and active compound of formula I above 10, with the exception of lactose.  
     
     
         3 . A composition according to  claim 1  wherein the first formulation does not contain polyols having a molecular weight of less than 300 in a molar ratio between polyol and active compound of formula I above 5.  
     
     
         4 . A composition according to  claim 1  wherein the first formulation does not contain polyols having a molecular weight of less than 300.  
     
     
         5 . A composition according to  claim 1  wherein the first formulation does not contain polyols having a molecular weight of less than 950 in a molar ratio between polyol and active compound of formula I above 5, with the exception of lactose.  
     
     
         6 . A composition according to  claim 1  wherein the first formulation does not contain polyols having a molecular weight of less than 950, with the exception of lactose.  
     
     
         7 . A composition according to  claim 1  wherein the formulations are prepared in the form of powders, granules, solutions or suspensions.  
     
     
         8 . A composition according to  claim 1  wherein the polyol in the second formulation is mannitol.  
     
     
         9 . A composition according to  claim 1  wherein the polyol in the second formulation is a polysaccharide.  
     
     
         10 . A composition according to  claim 1  wherein at least one of the formulations further contains an alkalinizing agent.  
     
     
         11 . A composition according to  claim 10  wherein the alkalinizing agent is sodium citrate.  
     
     
         12 . A composition according to  claim 1  wherein the first formulation further contains one or more excipients selected from cyclodextrins, colloidal anhydrous silica, microcristalline cellulose, magnesium stearate, flavors or colorants.  
     
     
         13 . A composition according to  claim 1  wherein the first formulation further contains non-polyol sweetening agents such as acesulfame K, aspartame, saccharine, saccharine sodium or cyclamate.  
     
     
         14 . A composition according to  claim 1  wherein the active compound in the first formulation is cetirizine dihydrochloride, levocetirizine dihydrochloride or efletirizine dihydrochloride.  
     
     
         15 . A composition according to  claim 1  wherein it is in the form of a chewing gum, tablet or effervescent tablet.  
     
     
         16 . A composition according to  claim 15  in the form of a multi-layer tablet wherein each of the layers is prepared from one of the formulations.  
     
     
         17 . A composition according to  claim 16  in the form of a multi-layer tablet wherein an inert layer separates the layers prepared from the two formulations.  
     
     
         18 . A composition according to  claim 15  wherein it is a tablet having an inner core prepared from one of the formulation and an outer shell prepared from the other formulation.  
     
     
         19 . A composition according to  claim 15  wherein it is a chewing gum that comprises 
 a core made from the first formulation and additionally containing the gum base, and    a coating made from the second formulation.    
     
     
         20 . A composition according to  claim 15  wherein it is a chewing gum that comprises 
 a core made from the second formulation and additionally containing the gum base, and    a coating made from the first formulation.    
     
     
         21 . A composition according to  claim 1  wherein it is a dry syrup prepared from a mixture of two types of granules wherein one type of granules is made by compaction of the first formulation and the other type of granules is made by compaction of the second formulation.  
     
     
         22 . A method of preparing a composition according to  claim 1  by separately preparing the first formulation, preparing the second formulation and combining the two formulations.