Enteric-coated proliposomal formulations for poorly water soluble drugs

Abstract

This invention relates to enteric-coated proliposomal formulations for oral medicaments. In particular, it relates to an enteric-coated proliposomal oral drug delivery system for poorly water soluble drugs and methods for making the same. The drug delivery system comprises a pharmaceutical agent, a phospholipid and an enteric coating material. The present invention provides enhanced stability and bioavailability for orally administered drugs.

1 - 38 . (Canceled).  
     
     
         39 . A method of making a formulation suitable for administration to a patient, consisting essentially of: 
 providing one or more phospholipids;    providing one or more biologically active agents;    exposing simultaneously at least a portion of said one or more biologically active agents and at least a portion of said one or more phospholipids to a non-aqueous solvent;    removing said non-aqueous solvent, thereby making a powder, wherein said powder comprises said one or more phospholipids and said one or more biologically active agents; and    coating said powder with one or more enteric coatings, thereby making coated particles, wherein said one or more enteric coatings contacts at least a portion of said powder.    
     
     
         40 . The method of  claim 39 , further comprising preparing said coated particles into a dosage form suitable for administration to a patient.  
     
     
         41 . The method of  claim 39 , further comprising preparing said coated particles into a suspension.  
     
     
         42 . The method of  claim 39 , further comprising preparing said coated particles into a tablet.  
     
     
         43 . The method of  claim 39 , further comprising preparing said coated particles into a capsule.  
     
     
         44 . The method of  claim 39 , wherein said biologically active agent is testosterone.  
     
     
         45 . The method of  claim 39 , wherein said biologically active agent is famotidine.  
     
     
         46 . The method of  claim 39 , wherein said biologically active agent is halofantrine.  
     
     
         47 . The method of  claim 39 , wherein said biologically active agent is glyburide.  
     
     
         48 . The method of  claim 39 , wherein said biologically active agent is a time-released agent.  
     
     
         49 . The method of  claim 39 , wherein said phospholipid is a phosphatidyl phospholipid.  
     
     
         50 . The method of  claim 39 , wherein said phospholipid is selected from the group consisting of one or more of the following: distearoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, dimyristoyl phosphatidylcholine, egg PC, soy PC, DMPG, DMPA, DPPG, DPPA, DSPG, DSPA, phosphatidylserine and sphigomyelin.  
     
     
         51 . The method of  claim 39 , further comprising adding a plasticizer.  
     
     
         52 . The method of  claim 39 , further comprising adding a plasticizer, wherein said plasticizer is selected from the group consisting of one or more of the following: phthalate esters, citrate esters and triacetin.  
     
     
         53 . The method of  claim 39 , wherein coating said powder with one or more enteric coatings comprises spraying said powder.  
     
     
         54 . The method of  claim 39 , further comprising combining at least one additional ingredient with said biologically active agent.  
     
     
         55 . The method of  claim 39 , further comprising combining at least one additional ingredient with said biologically active agent, wherein said at least one additional ingredient is selected from the group consisting of one or more of the following: carriers, diluents and lubricants.  
     
     
         56 . The method of  claim 39 , further comprising combining at least one additional ingredient with said biologically active agent, wherein said at least one additional ingredient is selected from the group consisting of one or more of the following: microcrystalline cellulose, starch, lactose, talc, mannitol, polyethylene glycol, polyvinylpyrrolidone, hydroxypropylmethyl cellulose, ethyl cellulose, fatty acids, fatty acid salts, glyceryl behenate, dextrose and dicalcium phosphate.  
     
     
         57 . A method of making a formulation suitable for administration to a patient, comprising: 
 providing at least one phospholipid;    providing at least one biologically active agent, wherein said one or more biologically active agents requires greater than about thirty parts aqueous solvent per one part solute to dissolve;    exposing at least a portion of said at least one biologically active agent and at least a portion of said at least one phospholipid to a non-aqueous solvent;    evaporating said non-aqueous solvent, thereby making a powder;    coating said powder with one or more enteric coatings without having exposed said biologically active agent to an aqueous solvent, thereby making coated particles, wherein said one or more enteric coatings contacts at least a portion of said powder; and    preparing said coated particles into a dosage form suitable for administration to a patient.    
     
     
         58 . A method of making a composition for delivery of a chemical agent, comprising: 
 providing one or more phospholipids;    providing one or more chemical agents, wherein said one or more chemical agents is labile in an aqueous phase;    exposing at least a portion of said one or more chemical agents and at least a portion of said one or more phospholipids to a non-aqueous solvent;    removing said non-aqueous solvent, thereby making a powder, wherein said non-aqueous solvent is removed by evaporation;    covering said powder with one or more enteric coatings, thereby making coated particles, wherein said one or more enteric coatings contacts at least a portion of said powder, and wherein one or more chemical agents is not exposed to an aqueous phase prior to application of the coating; and    synthesizing said coated particles into a form suitable for delivery of said chemical agent.