Emulsions as solid dosage forms for oral administration

Abstract

Novel emulsion compositions which improve the rate and/or extent of absorption of drugs are disclosed. The novel emulsion compositions of the present invention include drug-containing emulsions adsorbed onto solid particles which may be further formulated into solid dosage forms, methods of preparing such emulsion compositions and their uses thereof. The emulsion compositions and their dosage forms improve the drug-load and the bioavailability of a wide range of drugs including drugs that are known or suspected of having poor bioavailability by the utilization of several different mechanisms.

1 . An emulsion composition comprising: a free-flowing, compressible particle which is an admixture of a drug-containing emulsion having a viscosity of between about 1 cps and about 400,000 cps and wherein said emulsion has globules having diameters of greater than 100 nm.  
     
     
         2 . The emulsion composition of  claim 1 , wherein the drug-containing emulsion has a viscosity of between about 400 cps and about 200,000 cps.  
     
     
         3 . The emulsion composition of  claim 1 , wherein the drug-containing emulsion having between about 2% and about 50% drug by weight based on the weight of the formulation.  
     
     
         4 . The emulsion composition of  claim 1 , wherein said drug-containing emulsion is an oil-in-water emulsion.  
     
     
         5 . The emulsion composition of  claim 1  wherein said drug-containing emulsion is a water-in-oil emulsion.  
     
     
         6 . The emulsion composition of  claim 1 , wherein said drug-containing emulsion is a self-emulsifying drug delivery system which converts to an emulsion in vivo.  
     
     
         7 . The emulsion composition of  claim 1 , wherein said solid particle is selected from the group consisting of kaolin, bentonite, hectorite, colloidal magnesium aluminum silicate, silicon dioxide, magnesium trisilicate, aluminum hydroxide, magnesium hydroxide, magnesium oxide and talc.  
     
     
         8 . The emulsion composition of  claim 1 , wherein the compressibility of the free-flowing compressible powder is further improved by the addition of direct compression tableting excipients.  
     
     
         9 . The emulsion composition of  claim 1 , wherein said drug contained in said emulsion is a drug that displays poor bioavailability in the gastrointestinal tract of a mammal, when said drug is administered in a conventional dosage form that does not contain any penetration enhancer or other mechanism to enhance drug absorption.  
     
     
         10 . The emulsion composition of  claim 1 , wherein said drug-containing emulsion includes a drug selected from the group consisting of peptides, proteins, oligonucleotides and other biological molecules.  
     
     
         11 . The emulsion composition of  claim 1 , wherein said drug-containing emulsion includes a nutritional supplement.  
     
     
         12 . The emulsion composition of  claim 1 , wherein said drug-containing emulsion includes a drug selected from the group consisting of acyclovir; auranofin; bretylium; cytarabine; doxepin; doxorubicin; hydralazine; ketamine; labetalol; mercaptopurine; methyldopa; nalbuphine; nalozone; pentoxifylline; pryridostigmine; terbutaline; verapamil; buserelin; calcitonin; cyclosporin; heparin; and oxytocin.  
     
     
         13 . An emulsion composition comprising: a free flowing, compressible particle which is an admixture of a drug-containing emulsion having between about 2% and about 50% drug by weight based on the weight of the finished formulation, said emulsion having globules having diameters of greater than 100 nm.  
     
     
         14 . The emulsion composition of  claim 13 , wherein said emulsion has a viscosity of between 1 cps and 400,000 cps.  
     
     
         15 . The emulsion composition of  claim 14 , wherein said emulsion has a viscosity of between about 120 nm and 70 μM.  
     
     
         16 . The emulsion composition of  claim 13 , wherein said particle is an absorbent powder and wherein said drug-containing emulsion is adsorbed on said particle.  
     
     
         17 . A solid dosage form for the administration of a therapeutically effective amount of a drug, comprising: 
 the emulsion composition of claims  1  or  13  and, optionally, at least one filler.    
     
     
         18 . The solid dosage form of  claim 17 , wherein said solid dosage form is a tablet for oral administration.  
     
     
         19 . The solid dosage form of  claim 17 , wherein said solid dosage form is a capsule for oral administration.  
     
     
         20 . The solid dosage form of  claim 17 , wherein said solid dosage form is a tablet for intra-oral administration, wherein said tablet is allowed to disintegrate in the oral cavity of a mammal, wherein the constituents of the tablet can be swallowed without the consumption of water or other liquid to assist swallowing.  
     
     
         21 . The solid dosage form of  claim 17 , further comprising a bioadhesive.  
     
     
         22 . The solid dosage form of  claim 17 , wherein said solid dosage form is a tablet for vaginal administration.  
     
     
         23 . The solid dosage form of  claim 17 , wherein said sold dosage form is a suppository for vaginal administration.  
     
     
         24 . The solid dosage form of  claim 17 , wherein said solid dosage form is a suppository for rectal administration.  
     
     
         25 . The solid dosage form of  claim 17 , further comprising an enteric coating maintained over said dosage form; wherein said enteric coating prevents the release of said drug-containing emulsion until a time at which said dosage form reaches a target area following oral administration.  
     
     
         26 . The solid dosage form of  claim 25 , wherein the enteric coating is selected from materials of the group consisting of a methacrylic acid copolymer, sugar, gelatin, hydroxypropyl cellulose or hydroxypropylmethyl cellulose phthalate, cellulose acetate phthalate, polyvinylacetate phthalate, methacrylic acid copolymer, shellac, hydroxypropylmethylcellulose succinate, cellulose acetate trimellitate, and their mixtures thereof.  
     
     
         27 . The solid dosage form of  claim 17 , wherein said solid dosage form further comprises at least one effervescent agent.  
     
     
         28 . The solid dosage form of  claim 17 , further comprising at least one disintegration agent; wherein said disintegration agent causes rapid dispersion of said drug-containing emulsion to a target area following oral administration.  
     
     
         29 . The solid dosage form of  claim 17 , further comprising a pH adjusting substance.  
     
     
         30 . The solid dosage form of  claim 17 , wherein said drug-containing emulsion includes a drug selected from the group consisting of peptides, proteins, oligonucleotides and other biological molecules.  
     
     
         31 . The solid dosage form of  claim 17 , wherein said drug-containing emulsion includes a nutritional supplement.  
     
     
         32 . The solid dosage form of  claim 17 , wherein said drug-containing emulsion includes a drug selected from the group consisting of acyclovir; auranofin; bretylium; cytarabine; doxepin; doxorubicin; hydralazine; ketamine; labetalol; mercaptopurine; methyldopa; nalbuphine; nalozone; pentoxifylline; pryridostigmine; terbutaline; verapamil; buserelin; calcitonin; cyclosporin; heparin; and oxytocin.  
     
     
         33 . The solid dosage form of  claim 17 , further comprising at least one filler, disintegration agent, effervescent agent or a pH adjusting substance.  
     
     
         34 . The solid dosage form of  claim 33 , wherein said drug is selected from the group consisting of acyclovir; auranofin; bretylium; cytarabine; doxepin; doxorubicin; hydralazine; ketamine; labetalol; mercaptopurine; methyldopa; nalbuphine; nalozone; pentoxifylline; pryridostigmine; terbutaline; verapamil; buserelin; calcitonin; cyclosporin; heparin; and oxytocin.  
     
     
         35 . A method for preparing an emulsion composition, comprising the steps of: 
 preparing a drug-containing emulsion and converting said drug-containing emulsion into a free-flowing, compressible powder by admixing said drug-containing emulsion with a solid particle.    
     
     
         36 . A method for preparing a solid dosage form for the oral administration of a therapeutically effective amount of a drug, comprising the steps of: 
 preparing a drug-containing emulsion having a viscosity of between about 1 cps and about 400,000 cps and wherein said emulsion globules has diameters of greater than 100 nm; converting said drug-containing emulsion into a solid by admixing said drug-containing emulsion with solid particles and compressing said solid, with the optional addition of an excipient, into a solid dosage form.    
     
     
         37 . A stable emulsion composition which is the product of the process of: 
 preparing a drug-containing emulsion; converting said drug-containing emulsion into a powder by admixing said drug-containing emulsion with a solid particulate adsorbent.    
     
     
         38 . A method of administering an emulsion composition of claims  1  or  13  to a mammal comprising the steps of preparing the emulsion composition of claims  1  or  13  and administering said emulsion composition to said mammal.  
     
     
         39 . A method is claimed in  claim 38  further comprising the step of incorporating said emulsion composition into a solid dosage form, said step of administering said emulsion composition to said mammal including the step of administering the solid dosage form to the mammal.