Chemical delivery device

Abstract

The invention provides a controlled release dissolution and diffusion devices which can deliver an active ingredient at a constant or controlled-variable rate comprising an active ingredient and dissolution modifiers and/or an insoluble matrix. The compressed core is coated, except for at least one exposed face, with a coating containing an insoluble polymer or a mixture of an insoluble polymer and pore-forming elements said pore-forming elements having a dissolution rate slower that the release rate so that the pore formation is completed after release of the active ingredients and the residual inert structures disintegrate.

What is claimed is:  
     
         1 . A dissolution-controlled chemical delivery device providing controlled variable release of at least one biologically active ingredient into a medium throughout a substantial portion of a delivery period which composition comprises 
 (i) a shaped core (a) having at least one release face wherein dissolution at said face causes a surface area of said face to vary throughout a substantial portion of the delivery period, and (b) containing the biologically active ingredient mixed with at least one dissolution regulator operable to release the biologically active ingredient from said release face, and;    (ii) a coating surrounding and adhering to said core except the release face(s), said coating containing an insoluble polymer or a mixture of an insoluble polymer and pore-forming elements operable to create channels in said impermeable coating to permit disintegration of the coating after release of said active ingredient is completed.    
     
     
         2 . A device according to  claim 1  wherein said core is a circadian configuration.  
     
     
         3 . A device according to  claim 2  which comprises two release faces.  
     
     
         4 . A device according to  claim 2  wherein said polymer coating is selected from a group consisting of ethyl cellulose, cellulose acetate, cellulose acetate butyrate and cellulose acetate phthalate, polyvinyl alcohol, polyvinyl acetate and methacrylic acid copolymers.  
     
     
         5 . A device according to  claim 2  wherein said pore-forming element is selected form a group consisting of dextrose, fructose, glucose, dextrates, sorbitol and carbowax.  
     
     
         6 . A device according to  claim 2  wherein said dissolution regulator is selected from a group consisting of hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, methyl cellulose, soluble modified starches, gelatin, and acacia.  
     
     
         7 . A device according to  claim 2  where the active ingredient is a pharmaceutical agent for human use.  
     
     
         8 . A device according to  claim 7  where the active ingredient is selected from a group consisting of psychotherapeutic agents, antidiabetic drugs, anticonvulsants, cardiovascular drugs, stroke treatment agents, respiratory therapies, anti-infective agents, migraine therapies, urinary tract agents, contraceptives, analgesics, cholesterol reducers, antiarthritic agents, gastrointestinal products, muscle-relaxants, muscle-contractants, anti-Parkinson agents, anti-inflammatory agents, hormonal agents, diuretics, electrolytes, serotonin agonists and antagonists H2-antagonists muscle relaxants.  
     
     
         9 . A device according to  claim 8  where the active ingredient is selected based on a suitable half-life and adsorption characteristics from a group consisting of aspirin, bupropion hydrochloride, buspirone hydrochloride, carbamazepine, carbidopa, cephalosporin, cimetidine hydrochloride, citalopram hydrobromide, clarithromycin, clonidine, diclofenac sodium, diltiazem hydrochloride, dipyridamole, divalproex sodium, doxazosin mesylate, enalapril maleate, ethinyl estradiol, etodolac, fexofenadine hydrochloride, glipizide, haloperidol, ibuprofen, indomethacine, isosorbide dinitrate, isradipine, ketoprofen, labetalol, lansoprazole, levodopa, lithium carbonate, loratidine, lovastatin, methascopolomine chloride, metformin hydrochloride, metronidazole, methylphenidate hydrochloride, metoprolol succinate, morphine sulfate, naproxen sodium, nifedipine, nisoldipine, norethindrone acetate, omeprazole, oxybutynin chloride, oxycodone hydrochloride, penicillin, pentoxifylline, potassium chloride, pseudoephedrine hydrochloride, rabeprazole sodium, ranitidine hydrochloride, salbutamol, terfenadine, theophylline, tramadol hydrochloride, trandolapril, venlafaxine hydrochloride, verapamil hydrochloride, and alternative or pharmaceutically acceptable salts thereof.  
     
     
         10 . A device according to  claim 2  where said active ingredient is a pharmaceutical agent for veterinary use.  
     
     
         11 . A device according to  claim 2  where said active ingredient is an insecticide or fungicide.  
     
     
         12 . A device according to  claim 2  where said active ingredient is a biocide or disinfectant.  
     
     
         13 . A process for the preparation of a chemical delivery device according to  claim 2  by dry granulation process comprising the steps of: 
 (a) blending said active ingredient and a dissolution regulator and optionally with a diluent;  
 (b) optionally milling and sieving the resulting blend with a mesh size suitable for the specific application;  
 (c) mixing said blend with a soluble or insoluble lubricant and compressing said blend into tablet with an appropriate shape in a punch machine;  
 (d) coating said tablet with a coating containing an insoluble polymer or a mixture of an insoluble polymer and pore-forming elements using a compression-coating machine.  
 
     
     
         14 . A process for the preparation of a chemical delivery device according to  claim 2  by wet granulation process comprising: 
 (a) blending said biologically active ingredient and a dissolution regulator with water, an organic solvent or a mixture of water and an organic solvent and optionally with a diluent;  
 (b) drying the resulting blend at an appropriate temperature, milling and sieving the resulting blend with a mesh size suitable for the specific application;  
 (c) mixing said blend with a soluble or insoluble lubricant and compressing the blend into tablet into an appropriate shape in a punch machine;  
 (d) coating said tablet with a mixture containing an insoluble polymer or a mixture of an insoluble polymer and pore-forming elements using a compression-coating machine.  
 
     
     
         15 . A method of delivering an active ingredient with a controlled variable release of an active compound into a medium comprising: 
 (a.) incorporating at least one biologically active ingredient into a tablet having: 
 (i) a shaped core (a) having at least one planar release face wherein the dissolution of said face causes at least one of the dimensions of said face to vary thereby increasing or decreasing the surface area of said face throughout a substantial portion of the delivery period wherein said core is a circadian configuration, and (b) containing a compressed mixture of the biologically active ingredient homogeneously mixed with at least one dissolution regulator operable to release the biologically active ingredient from said release face; and,  
 (ii) a coating surrounding and adhering to said core except the release face(s), said coating containing an insoluble polymer or a mixture of an insoluble polymer and pore-forming elements operable to create channels in said impermeable coating to permit disintegration of the coating after release of said active ingredient is completed said coating disintegrating over a substantially longer period of time than is required for said dissolution regulator to release said biologically active ingredient; and,  
   (b) placing said tablet in a fluid medium in need of the presence of said active ingredient.