Multiplex drug delivery system suitable for oral administration

Abstract

A multiplex drug delivery system suitable for oral administration containing at least two distinct drug dosage packages, which exhibit equivalent dissolution profiles for an active agent when compare to one another and when compared to that of the entire multiplex drug delivery unit, and substantially enveloped by a scored film coating that allows the separation of the multiplex drug delivery system into individual drug dosage packages can provide a convenient and cost effective drug delivery unit, particularly for patients with a regimen of prescribed dosages that varies during their treatment period.

What is claimed is:  
     
         1 . A multiplex drug delivery system suitable for oral administration comprising at least two immediate-release compartments substantially enveloped by a scored extended-release compartment, which facilitates separation of said multiplex drug delivery system into individual drug dosage packages.  
     
     
         2 . The multiplex drug delivery system of  claim 1 , wherein each of said immediate-release compartments further comprises an effective amount of an active agent, or a pharmaceutically acceptable salt thereof, and wherein said scored extended-release compartment further comprises an effective amount of an active agent, or a pharmaceutically acceptable salt thereof, in a compressed blend with a combination of a hydrophilic polymer and a hydrophobic material, and wherein each of said individual drug dosage packages exhibits an equivalent release profile for said active agent when compared to one another or when compared to said multiplex drug delivery system in its entirety.  
     
     
         3 . The multiplex drug delivery system of  claim 1 , wherein each of said immediate-release compartments further comprises an effective amount of an active agent, or a pharmaceutically acceptable salt thereof, in a compressed blend with a polymer.  
     
     
         4 . The multiplex drug delivery system of  claim 1 , wherein said scored extended-release compartment further comprises an effective amount of an active agent, or a pharmaceutically acceptable salt thereof, in a compressed blend with a combination of a hydrophilic polymer and a hydrophobic material.  
     
     
         5 . The multiplex drug delivery system of  claim 2 , wherein said active agent is a drug.  
     
     
         6 . The multiplex drug delivery system of  claim 5 , wherein said drug is a therapeutic drug.  
     
     
         7 . The multiplex drug delivery system of  claim 5 , wherein said drug is a prophylactic drug.  
     
     
         8 . The multiplex drug delivery system of  claim 5 , wherein said drug is selected from the group consisting of diltiazem, trapidil, urapidil, benziodarone, dipyridamole, isosorbide mononitrate, and lidoflazine.  
     
     
         9 . The multiplex drug delivery system of  claim 5 , wherein said drug is selected from the group consisting of non-steroidal antiinflammatory drugs (NSAIDs) and steroidal antiinflammatory drugs.  
     
     
         10 . The multiplex drug delivery system of  claim 9 , wherein said steroidal antiinflammatory drug is selected from the group consisting of diclofenac sodium, ibuprofen, ketoprofen, diflunisal, piroxicam, motrin, and naproxen.  
     
     
         11 . The multiplex drug delivery system of  claim 5 , wherein said drug is selected from the group consisting of acetaminophen, aldosterone, alprenolol, amitryptyline, aspirin, beclomethasone, diproprionate, bromocriptine, butorphanol tartrate, chlormethiazole, chlorpheniramine, chlorpromazine HCl, cimetidine, codeine, cortisone, cyclobenzamine HCl, desmethylimipramine, dextropropoxyphene, dihydroergotamine, diltiazem HCl, dobutamine HCl, domperidone, dopamine HCl, doxepin HCl, epinephrine, ergoloid mesylates, ergotamine tartrate estradiol, ethinylestradiol, flunisolide, fluorouracil, flurazepam HCl, 5-fluoro-21-deoxyuridine, furosemide, glipizide, glyburide, glyceryl trinitrate, guanethidine sulfate, hydralazine HCl, imipramine HCl, indoramin, isoethorine HCl, isoethrine mesylate, isoprenaline, isoproterenol sulfate, isosorbide dinitrate, levallorphan tartrate, levodopa, lidocaine HCl, lignocaine, lorcainide, meperidine HCl, 6-mercaptopurine, metaproterenol sulfate, methoxamine HCl, methylphenidate, methylpreonisolone, methyltestosterone mesylate, metoclopramide, metoprolol tartrate, morphine sulfate, nalbuphine HCl, naloxone HCl, neostigmine, nifedipine, nitrendipine, nitroglycerin, norepinephrine bitartrate, norethindrone, nortriptylene HCl, oxprenolol, oxyphenbutazone, penicillamine, pentazocine HCl, pentazocine lactate, pentobarbital, petnidine, phenacetin, phentolamine HCl, phentolamine mesylate, phenylephrine HCl, phenylephrine bitartrate, phenytoin, pindolal, prazosin, prednisone, progesterone, propoxyphene HCl, propoxyphene napsylate, propranolol HCl, quinidine, reserpine, ritodrine HCl, salicylamide, salbutamol, secobarbital, testosterone, terbutaline, timolol maleate, tolbutamide, and verapamil HCl.  
     
     
         12 . The multiplex drug delivery system of  claim 5 , wherein said active agent is isosorbide-5-mononitrate.  
     
     
         13 . The multiplex drug delivery system of  claim 2 , wherein said active agent exhibits the following in vitro dissolution profile when measured in a type 2 dissolution apparatus (paddle) according to U.S. Pharmacopeia XXII at 37° C.±0.5° C. in deionized water at 75 rotations per minute: 
 (a) from about 0% to about 90% of said active agent is released between 1 hour and 16 hours of measurement in said apparatus; and  
 (b) from about 0% to about 100% of said active agent is released between 1.5 hours and 28 hours after measurement in said apparatus.  
 
     
     
         14 . The multiplex drug delivery system of  claim 13 , wherein said active agent exhibits the following in vitro dissolution profile when measured in a type 2 dissolution apparatus (paddle) according to U.S. Pharmacopeia XXII at 37° C.±0.5° C. in deionized water at 75 rotations per minute: 
 (a) from about 10% to about 75% of said active agent is released between 1 hour and 5 hours of measurement in said apparatus; and  
 (b) no less than about 90% of said active agent is released after 6 hours of measurement in said apparatus.  
 
     
     
         15 . The multiplex drug delivery system of  claim 14 , wherein said active agent is isosorbide-5-mononitrate.  
     
     
         16 . The multiplex drug delivery system of  claim 3 , wherein said polymer is selected from the group consisting of alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, guar gum, magnesium aluminum silicate, methylcellulose, microcrystalline cellulose, cellulose, pregelatinized starch, sodium alginate, starch, ethylcellulose, gelatin, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polymethacrylates, povidone, shellac, and zein.  
     
     
         17 . The multiplex drug delivery system of  claim 16 , wherein said polymer is selected from the group consisting of colloidal silicon dioxide, microcrystalline cellulose, and hydroxypropyl methylcellulose.  
     
     
         18 . The multiplex drug delivery system of  claim 2 , wherein said hydrophilic polymer is selected from the group consisting of carboxymethylcellulose, guar gum, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, and povidone.  
     
     
         19 . The multiplex drug delivery system of  claim 18 , wherein said hydrophilic polymer is hydroxypropyl methylcellulose.  
     
     
         20 . The multiplex drug delivery system of  claim 2 , wherein said hydrophobic material is selected from the group consisting of carnauba wax, ethylcellulose, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, microcrystalline wax, polymethacrylates, and stearic acid.  
     
     
         21 . The multiplex drug delivery system of  claim 20 , wherein said hydrophobic material is hydrogenated vegetable oil.  
     
     
         22 . A method for preparing a multiplex drug delivery system suitable for oral administration comprising the steps of: 
 (a) combining an effective amount of an active agent, or a pharmaceutically acceptable salt thereof, and a polymer to form at least two immediate-release compartments;    (b) combining an effective amount of an active agent, or a pharmaceutically acceptable salt thereof, and a hydrophilic polymer and a hydrophobic material to form an extended-release compartment;    (c) press coating said extended-release compartment to substantially envelop said at least two immediate-release compartments, and    (d) scoring said extended-release compartment such that said immediate-release compartments are separable.    
     
     
         23 . The method of  claim 22 , wherein said combining is selected from the group consisting of blending, perforated pan coating, fluidized particle coating, wet granulation, fluid-bed granulation, and dry granulation.  
     
     
         24 . The method of  claim 22 , wherein said active agent is a drug.  
     
     
         25 . The method of  claim 24 , wherein said drug is a therapeutic drug.  
     
     
         26 . The method of  claim 24 , wherein said drug is a prophylactic drug.  
     
     
         27 . The method of  claim 24 , wherein said drug is selected from the group consisting of diltiazem, trapidil, urapidil, benziodarone, dipyridamole, isosorbide mononitrate, and lidoflazine.  
     
     
         28 . The method of  claim 24 , wherein said drug is selected from the group consisting of non-steroidal antiinflammatory drugs (NSAIDs) and steroidal antiinflammatory drugs.  
     
     
         29 . The method of  claim 28 , wherein said steroidal antiinflammatory drug is selected from the group consisting of diclofenac sodium, ibuprofen, ketoprofen, diflunisal, piroxicam, motrin, and naproxen.  
     
     
         30 . The method of  claim 24 , wherein said drug is selected from the group consisting of acetaminophen, aldosterone, alprenolol, amitryptyline, aspirin, beclomethasone, diproprionate, bromocriptine, butorphanol tartrate, chlormethiazole, chlorpheniramine, chlorpromazine HCl, cimetidine, codeine, cortisone, cyclobenzamine HCl, desmethylimipramine, dextropropoxyphene, dihydroergotamine, diltiazem HCl, dobutamine HCl, domperidone, dopamine HCl, doxepin HCl, epinephrine, ergoloid mesylates, ergotamine tartrate estradiol, ethinylestradiol, flunisolide, fluorouracil, flurazepam HCl, 5-fluoro-21-deoxyuridine, furosemide, glipizide, glyburide, glyceryl trinitrate, guanethidine sulfate, hydralazine HCl, imipramine HCl, indoramin, isoethorine HCl, isoethrine mesylate, isoprenaline, isoproterenol sulfate, isosorbide dinitrate, levallorphan tartrate, levodopa, lidocaine HCl, lignocaine, lorcainide, meperidine HCl, 6-mercaptopurine, metaproterenol sulfate, methoxamine HCl, methylphenidate, methylpreonisolone, methyltestosterone mesylate, metoclopramide, metoprolol tartrate, morphine sulfate, nalbuphine HCl, naloxone HCl, neostigmine, nifedipine, nitrendipine, nitroglycerin, norepinephrine bitartrate, norethindrone, nortriptylene HCl, oxprenolol, oxyphenbutazone, penicillamine, pentazocine HCl, pentazocine lactate, pentobarbital, petnidine, phenacetin, phentolamine HCl, phentolamine mesylate, phenylephrine HCl, phenylephrine bitartrate, phenytoin, pindolal, prazosin, prednisone, progesterone, propoxyphene HCl, propoxyphene napsylate, propranolol HCl, quinidine, reserpine, ritodrine HCl, salicylamide, salbutamol, secobarbital, testosterone, terbutaline, timolol maleate, tolbutamide, and verapamil HCl.  
     
     
         31 . The method of  claim 24 , wherein said active agent is isosorbide-5-mononitrate.  
     
     
         32 . The method of  claim 24 , wherein said polymer is selected from the group consisting of alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, guar gum, magnesium aluminum silicate, methylcellulose, microcrystalline cellulose, cellulose, pregelatinized starch, sodium alginate, starch, ethylcellulose, gelatin, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polymethacrylates, povidone, shellac, and zein.  
     
     
         33 . The method of  claim 32 , wherein said polymer is selected from the group consisting of colloidal silicon dioxide, croscarmellose sodium, microcrystalline cellulose, and hydroxypropyl methylcellulose.  
     
     
         34 . The method of  claim 24 , wherein said hydrophilic polymer is selected from the group consisting of carboxymethylcellulose, guar gum, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, and povidone.  
     
     
         35 . The method of  claim 34 , wherein said hydrophilic polymer is hydroxypropyl methylcellulose.  
     
     
         36 . The method of  claim 24 , wherein said hydrophobic material is selected from the group consisting of carnauba wax, ethylcellulose, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, microcrystalline wax, polymethacrylates, and stearic acid.  
     
     
         37 . The method of  claim 36 , wherein said hydrophobic material is hydrogenated vegetable oil.