Ingestible formulations for transient, noninvasive reduction of gastric volume

Abstract

Provided are ingestible polymeric formulations and oral dosage forms for the reduction of gastric volume in the treatment of overweight and obese patients. The formulation includes an acid-sensitive, gelatin coating over a dehydrated hydrophilic polymer. When ingested, the acid-sensitive coating is quickly dissolved by gastric secretions and the hydrophilic polymer is exposed to the aqueous environment of the gastric milieu. The polymer absorbs water and expands to the point that will not allow the polymer to pass beyond the pyloric valve, and the expanded polymer is therefore trapped in the stomach.

What is claimed is:  
     
         1 . An oral dosage form useful for gastric volume reduction comprising a polymer that (i) swells upon absorbing water from gastric fluid to increase its size thereby promoting its gastric retention, (ii) maintains its physical integrity in a stomach for at least  2  hours, and (iii) is degradable by an intestinal enzyme or exposure to an intestinal pH, wherein the dosage form is in the form of a tablet or capsule that maintains the polymer in a packed mass prior to its ingestion and then rapidly disintegrates in the gastric fluid to permit the polymer to disperse in the stomach and wherein the dosage form does not contain a drug.  
     
     
         2 . The oral dosage form of  claim 1 , wherein the polymer is selected from the group consisting of polyvinyl alcohol, poly(ethyloxazoline), polyvinylacetate-polyvinylalcohol copolymers, poly(2-hydroxyethylacrylate), poly(2-hydroxyethylmethacrylate), polyacrylic acid, and copolymers thereof; polysaccharides, water soluble proteins, and polynucleic acids.  
     
     
         3 . The oral dosage form of  claim 2 , wherein the polysaccharides is selected from the group consisting of carboxymethyl cellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, chitosan, hyaluronic acid, xanthan gum, starch, maltodextrins, corn syrup, and alginates.  
     
     
         4 . The oral dosage form of  claim 2 , wherein the protein is albumin or gelatin.  
     
     
         5 . The oral dosage form of  claim 1 , wherein the polymer is crosslinked with a crosslinker.  
     
     
         6 . The oral dosage form of  claim 5 , wherein the crosslinker is a homobifunctional crosslinker or a heterobifunctional crosslinker.  
     
     
         7 . The oral dosage form of  claim 6 , wherein the crosslinker contains a reactive group selected from the group consisting of glycidyl ethers, substituted and unsubstituted N-hydroxy-succinimides, isocyanates, acids, esters, acid chlorides, maleimides, and acrylates.  
     
     
         8 . The oral dosage form of  claim 1 , wherein the polymer is cross linked through a crosslinker which provides the polymer with a degradation susceptibility towards an intestinal enzyme or an intestinal pH.  
     
     
         9 . The oral dosage form of  claim 5 , wherein the crosslinker is an oligoester.  
     
     
         10 . The oral dosage form of  claim 5 , wherein the crosslinker is a diacid that forms an alpha-omega ester linkage.  
     
     
         11 . The oral dosage form of  claim 5 , wherein the crosslinker is diacid chloride.  
     
     
         12 . The oral dosage form of  claim 5 , wherein the crosslinker is selected from the group consisting of polymers and copolymers of lactic acid, glycolic acid, trimethylene carbonate, and caprolactone.  
     
     
         13 . The oral dosage form of  claim 1 , wherein the polymer is non-covalently cross linked.  
     
     
         14 . The oral dosage form of  claim 1 , wherein the oral dosage form contains an enteric coating.  
     
     
         15 . The oral dosage form of  claim 1 , wherein the polymer degrades faster in the intestinal than in the stomach.  
     
     
         16 . The oral dosage form of  claim 1 , wherein the polymer degrades faster in an environment with intestinal pH than in an environment with gastric pH.  
     
     
         17 . The oral dosage form of  claim 1 , wherein the intestinal enzyme is selected from the group consisting of lipase, amylase, trypsin, chymotrypsin, elastase, carboxypeptidase, nucleases, aminopeptidases, disaccharidases, maltase, sucrase, and lactase.  
     
     
         18 . The oral dosage form of  claim 1 , wherein the polymer is a biocompatible polymer.  
     
     
         19 . The oral dosage form of  claim 1  further comprises an agent wherein the agent stabilizes the polymer in an gastric environment.  
     
     
         20 . The oral dosage form of  claim 1  further comprises an agent wherein the agent stabilizes the polymer in an gastric environment and is sensitive to an intestinal pH.  
     
     
         21 . A polymeric formulation comprising a hydrophilic polymer that (i) swells upon absorbing water from gastric fluid to increase its size thereby promoting its gastric retention, (ii) maintains its physical integrity in a stomach for at least 2 hours, and (iii) degrades faster in the intestine than in the stomach, wherein the polymer is crosslinked through a crosslinker which provides the polymer with a degradation susceptibility towards an intestinal enzyme or an intestinal pH.  
     
     
         22 . The polymeric formulation of  claim 21 , wherein the polymer is selected from the group consisting of polyvinyl alcohol, poly(ethyloxazoline), polyvinylacetate-polyvinylalcohol copolymers, poly(2-hydroxyethylacrylate), poly(2-hydroxyethylmethacrylate), polyacrylic acid, and copolymers thereof; polysaccharides, water soluble proteins, and polynucleic acids.  
     
     
         23 . The polymeric formulation of  claim 21 , wherein the polysaccharides are selected from the group consisting of carboxymethyl cellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, chitosan, hyaluronic acid, xanthan gum, starch, maltodextrins, corn syrup, and alginates.  
     
     
         24 . The polymeric formulation of  claim 21 , wherein the protein is albumin or gelatin.  
     
     
         25 . The polymeric formulation of  claim 21 , wherein the crosslinker is a homobifunctional crosslinker or a heterobifunctional crosslinker.  
     
     
         26 . The polymeric formulation of  claim 25 , wherein the crosslinker contains a reactive group selected from the group consisting of glycidyl ethers, substituted and unsubstituted N-hydroxy-succinimides, isocyanates, acids, esters, acid chlorides, maleimides, and acrylates.  
     
     
         27 . The polymeric formulation of  claim 21 , wherein the crosslinker is a diacid that forms an alpha-omega ester linkage.  
     
     
         28 . The polymeric formulation of  claim 21 , wherein the formulation contains an enteric coating.  
     
     
         29 . The polymeric formulation of  claim 21 , wherein the intestinal enzyme is selected from the group consisting of lipase, amylase, trypsin, chymotrypsin, elastase, carboxypeptidase, nucleases, aminopeptidases, disaccharidases, maltase, sucrase, and lactase.  
     
     
         30 . The polymeric formulation of  claim 21 , wherein the polymer degrades faster in an environment with intestinal pH than in an environment with gastric pH.  
     
     
         31 . The polymeric formulation of  claim 21 , wherein the polymer is in a form of polymeric matrix.  
     
     
         32 . The polymeric formulation of  claim 21 , wherein the polymer is in a form of particle.  
     
     
         33 . The polymeric formulation of  claim 21 , further comprises a drug dispersed in the polymer.  
     
     
         34 . The polymeric formulation of  claim 21 , wherein the formulation is an oral dosage form.  
     
     
         35 . The polymeric formulation of  claim 21 , wherein the formulation is a tablet or capsule.  
     
     
         36 . The polymeric formulation of  claim 21 , wherein the polymer is a biocompatible polymer.  
     
     
         37 . The polymeric formulation of  claim 21  further comprises an agent wherein the agent stabilizes the polymer in an gastric environment.  
     
     
         38 . The polymeric formulation of  claim 21  further comprises an agent wherein the agent stabilizes the polymer in an gastric environment and is sensitive to an intestinal pH.  
     
     
         39 . A method of reducing gastric volume comprising administering to a subject in need of such treatment an oral dosage form of  claim 1 .  
     
     
         40 . A method of reducing gastric volume comprising administering to a subject in need of such treatment a polymeric formulation of  claim 21 .  
     
     
         41 . A method of reducing gastric volume comprising administering to a subject in need of such treatment an oral dosage form of  claim 1  and optionally a formulation comprising an intestinal enzyme.  
     
     
         42 . The method of  claim 41 , wherein the intestinal enzyme is selected from the group consisting of lipase, amylase, trypsin, chymotrypsin, elastase, carboxypeptidase, nucleases, aminopeptidases, disaccharidases, maltase, sucrase, and lactase.  
     
     
         43 . A method of reducing gastric volume comprising administering to a subject in need of such treatment a polymeric formulation of  claim 21  and optionally a formulation comprising an intestinal enzyme.  
     
     
         44 . The method of  claim 43 , wherein the intestinal enzyme is selected from the group consisting of lipase, amylase, trypsin, chymotrypsin, elastase, carboxypeptidase, nucleases, aminopeptidases, disaccharidases, maltase, sucrase, and lactase.  
     
     
         45 . A method for delivering a drug comprising administering to a subject in need of the drug the polymeric formulation of  claim 21 , wherein the formulation further contains the drug dispersed in the polymer.  
     
     
         46 . The method of  claim 45 , wherein the drug is an antibiotic.