Gastro-retentive drug delivery system

Abstract

The invention relates to floating drug delivery systems(FDDS) that provide solutions to the particular problems often encountered with floating drug delivery systems described in the art. On such generally recognized problem is the vulnerability of the systems, especially damage to the gas-filled compartment making it accessible to water so as to impair its buoyancy, ultimately resulting in insufficient gastric residence time. The invention, in an aspect, provides a self-repairing FDDS that maintains its floating capacity after damaging. The floating drug delivery systems of the invention, furthermore,allow for incorporation of high loads of active ingredients. The floating drug delivery systems can be designed in such a way that release of active ingredient from the system occurs entirely independent from the pH of the fluid surrounding the system. Furthermore, the procedure of manufacturing the floating drug delivery system of the invention is simple and straightforward, and therefore economically attractive.

1 - 18 . (canceled) 
     
     
         19 . A floating drug delivery system (FDDS), comprising a particle having a hollow, gas-filled core bordered by a wall of at least one aqueous soluble, erodible, disintegrating or degradable polymer, the wall being surrounded by a coating comprising at least one active ingredient and a water-swellable polymer that swells upon contact with water. 
     
     
         20 . The floating drug delivery system according to  claim 19 , wherein the particle is a capsule. 
     
     
         21 . The floating drug delivery system according to  claim 19 , wherein the active ingredient is not nicotinamide. 
     
     
         22 . The floating drug delivery system according to  claim 19 , wherein the system maintains its release profile and floating properties when mechanically damaged or ruptured 
     
     
         23 . The floating drug delivery system according to  claim 19 , wherein the water-swellable polymer comprises hypromellose. 
     
     
         24 . The floating drug delivery system according to  claim 19 , wherein the coating comprises a water-swellable polymer other than hypromellose. 
     
     
         25 . The floating drug delivery system according to  claim 19 , wherein the water-swellable polymer is selected from the group consisting of hydrophilic cellulose derivatives, such as HPMC, HPC, MC, HEC, CMC, sodium-CMC); PVP; PVA; carboxyvinyl polymer (carbomer); poly(ethyleneoxide) (polyox WSR), alginates, pectins, guar gum, vinylpyrrolidone-vinyl acetate compolymer; dextrans; carrageenan; gellan;
 hyaluronic acid; pullulan; scleroglucan; xanthan; and xyloglucan.   
     
     
         26 . The floating drug delivery system according to  claim 19 , comprising one or more coating layers comprising a combination of HPMC and starch as coating material. 
     
     
         27 . The floating drug delivery system according to  claim 26 , having HPMC and starch in a ratio within the range of 8:1-1:1. 
     
     
         28 . The floating drug delivery system according to  claim 26 , comprising at least two active ingredient containing coating layers having distinct ratios of hypromellose and starch, the outer layer typically comprising a larger amount of hypromellose, relative to starch, than the inner layer. 
     
     
         29 . The floating drug delivery system according to  claim 19 , capable of remaining in the stomach for at least 6 hours and/or of releasing active ingredient to the stomach and proximal small intestine for at least 6 hours. 
     
     
         30 . The floating drug delivery system according to  claim 19 , wherein the coating is selected from the group consisting of coatings resistant to gastric juice, release-controlling coatings, and mixtures thereof. 
     
     
         31 . The floating drug delivery system according to  claim 30 , wherein the release-controlling coating comprises:
 (a) a swellable, poorly water-soluble or water-insoluble polymer;   (b) one or more enteric polymeric material(s);   (c) a mixture of at least two release controlling polymers;   (d) a mixture of an enteric polymer, and a release controlling polymer.   
     
     
         32 . The floating drug delivery system according to  claim 19 , having a density less than 0.95 g/cm 3 . 
     
     
         33 . The floating drug delivery system according to  claim 19 , having a density less than 0.8 g/cm 3 . 
     
     
         34 . A floating drug delivery system (FDDS), comprising a particle having a hollow, gas-filled core bordered by a wall of at least one aqueous soluble, erodible, disintegrating or degradable polymer, the wall being surrounded by a coating comprising at least one active ingredient. 
     
     
         35 . A method for providing a floating drug delivery system according to  claim 34 , comprising:
 (a) providing a gas-filled particle made of at least one aqueous soluble, erodible, disintegrating or degradable polymer;   (b) providing a coating dispersion comprising an active ingredient, a polymer, optionally additive(s), in a volatile solvent;   (c) applying at least one layer of dispersion on the surface of particle; and   (d) allowing the evaporation of the volatile solvent such that a layer comprising the active ingredient is formed at the surface of the particle.   
     
     
         36 . The method according to  claim 35 , wherein the particle is a capsule.