Dual drug dosage forms with improved separation of drugs

Abstract

Drug tablets that include a prolonged-release core and an immediate-release layer or shell are prepared with a thin barrier layer of drug-free polymer between the prolonged-release and immediate-release portions of the tablet. The barrier layer is penetrable by gastrointestinal fluid, thereby providing full access of the gastrointestinal fluid to the prolonged-release core, but remains intact during the application of the immediate-release layer, substantially reducing or eliminating any penetration of the immediate-release drug into the prolonged-release portion.

1 .- 42 . (canceled) 
     
     
         43 . A dosage form comprising:
 an immediate-release section comprising a solid layer adhering to a polymeric film, the solid layer comprising a first drug dispersed in a matrix that promotes immediate release of the first drug upon immersion of the dosage form in gastrointestinal fluid;   a prolonged-release section comprising a second drug dispersed in a solid matrix that releases the second drug by prolonged release upon immersion of the dosage form in gastrointestinal fluid;   a polymeric film adhering to a surface of the prolonged-release section, the polymeric film being penetrable by gastrointestinal fluid and devoid of both the first drug and the second drug;   wherein the dosage form delivers the first drug immediately upon ingestion and delivers the second drug by prolonged release, wherein prolonged release is defined as a release rate that is slow enough to leave at least about 40% of the second drug unreleased one hour after ingestion.   
     
     
         44 . The dosage form of  claim 43 , wherein the solid matrix is a member selected from the group consisting of celluloses, substituted celluloses, microcrystalline cellulose, polysaccharides, substituted polysaccharides, polyl(alkylene oxide)s, poly(vinyl alcohol), starch, starch-based polymers, crosslinked poly(acrylic acid)s, and substituted crosslinked poly(acrylic acid)s. 
     
     
         45 . The dosage form of  claim 43 , wherein the polymeric film is a member selected from the group consisting of poly(ethylene oxide), hydroxypropyl methyl cellulose, polyvinyl alcohol, combinations of poly(ethylene oxide) and hydroxypropyl methyl cellulose, and combinations of polyvinyl alcohol and poly(ethylene oxide). 
     
     
         46 . The dosage form of  claim 43 , wherein the weight ratio of the polymeric film to the solid matrix is from about 0.005:1 to about 0.2:1. 
     
     
         47 . The dosage form of  claim 43 , wherein the polymeric film and the immediate-release section constitute a shell that fully encases the prolonged-release section. 
     
     
         48 . The dosage form of  claim 43 , wherein the polymeric film and the immediate-release section cover a portion of the surface of the prolonged-release section, leaving the remainder of the prolonged-release section exposed. 
     
     
         49 . The dosage form of  claim 43 , wherein one of the first and second drugs is a diuretic and the other is a member selected from the group consisting of angiotensin converting enzyme inhibitors and angiotensin II antagonists. 
     
     
         50 . The dosage form of  claim 49 , wherein the diuretic is a loop diuretic. 
     
     
         51 . The dosage form of  claim 50 , wherein the loop diuretic is a member selected from the group consisting of furosemide, torsemide, ethacrynic acid, and bumetanide. 
     
     
         52 . The dosage form of  claim 49 , wherein the diuretic is a thiazide diuretic. 
     
     
         53 . The dosage form of  claim 52 , wherein the thiazide diuretic is a member selected from the group consisting of chlorothiazide, bendoflumethazide, hydroflumethazide, trichlorthiazide, chlorthalidone, indapamide, metolazone, quinethazone and hydrochlorthiazide. 
     
     
         54 . The dosage form of  claim 49 , wherein the diuretic is a potassium-sparing diuretic. 
     
     
         55 . The dosage form of  claim 54 , wherein the potassium-sparing diuretic is a member selected from the group consisting of amiloride hydrochloride and triamterene. 
     
     
         56 . The dosage form of  claim 43 , wherein the first drug is a member selected from the group consisting of lisinopril and losartan, and the second drug is a diuretic. 
     
     
         57 . The dosage form of  claim 43 , wherein the first drug is selected from the group consisting of glyburide, glipizide, and glitazone and the second drug is metformin hydrochloride. 
     
     
         58 . The dosage form of  claim 43 , wherein the first drug is pyridoxine hydrochloride, and the second drug is selected from the group consisting of atorvastatin, simvastatin, pravastatin, lovastatin, cerivastatin, rosuvastatin, and fluvastatin. 
     
     
         59 . The dosage form of  claim 43 , wherein the second drug is a member selected from the group consisting of metformin hydrochloride, vancomycin hydrochloride, captopril, erythromycin lactobionate, ranitidine hydrochloride, sertraline hydrochloride, ticlopidine hydrochloride, amoxicillin, cefuroxime axetil, cefaclor, clindamycin, doxifluridine, tramadol, fluoxitine hydrochloride, ciprofloxacin hydrochloride, gancyclovir, bupropion, lisinopril, cefaclor, saguinavir, ritonavir, nelfinavir, clarithromycin, azithromycin, ceftazidine, cyclosporin, digoxin, paclitaxel, iron salts, topiramate, and ketoconazole. 
     
     
         60 . The dosage form of  claim 43 , wherein the second drug is a member selected from the group consisting of lisinopril, enalapril, captopril, fosinopril, quinapril, ramipril, and benazepril. 
     
     
         61 . The dosage form of  claim 43 , wherein the second drug is selected from the group consisting of losartan, valsartan, candesartan, irbesartan, telmisartan, and eprosartan. 
     
     
         62 . The dosage form of  claim 43 , wherein the first drug is a sulfonylurea selected from the group consisting of glimepiride, glyburide, and glipizide, and the second drug is metformin hydrochloride.