Uniform films for rapid dissolve dosage form incorporating taste-masking compositions

Abstract

The present invention relates to rapid dissolve thin film drug delivery compositions for the oral administration of active components. The active components are provided as taste-masked or controlled-release coated particles uniformly distributed throughout the film composition. The compositions may be formed by wet casting methods, where the film is cast and controllably dried, or alternatively by an extrusion method.

1 . A drug delivery composition for making individual unit doses, in a self-supporting film dosage form, which individual unit doses contain a desired amount of at least one active, the composition comprising:
 a self-supporting cast film with the active substantially uniformly stationed therein comprising   a water-soluble or water swellable film-forming matrix comprising
 one or more water-soluble or water swellable polymers, the active and a taste-masking agent selected from the group consisting of flavors, sweeteners, flavor enhancers and combinations thereof, the active substantially uniformly stationed in the matrix and having a particle size of 200 microns or less; 
   wherein the matrix has a viscosity sufficient to aid in substantially maintaining non-self-aggregating uniformity of the active in the matrix while forming the self-supporting cast film;   wherein the matrix forms a self-supporting film without loss of substantial uniformity in the stationing of the active; and   wherein the substantial uniformity in the stationing of the active in the self-supporting film is measured by substantially equally sized individual unit doses which do not vary more than 10% from the desired amount of the active.   
     
     
         2 . The drug delivery composition of  claim 1 , wherein the active is selected the group consisting of opiates, opiate derivatives, analgesics, apomorphine, hormones, tadalafil, urinary tract agents, migraine treatments, alprazolam, biological response modifiers, and combinations thereof. 
     
     
         3 . The drug delivery composition of  claim 1 , wherein said active is selected from the group consisting of anxiolytics, central nervous system stimulants, ace-inhibitors, antianginal drugs, anti-arrhythmias, anti-asthmatics, anti-cholesterolemics, anesthetics, anti-convulsants, anti-depressants, anti-diabetic agents, anti-diarrhea preparations, antidotes, anti-histamines, anti-hypertensive drugs, anti-inflammatory agents, anti-lipid agents, anti-manics, anti-nauseants, anti-stroke agents, anti-thyroid preparations, anti-tumor drugs, anti-viral agents, acne drugs, alkaloids, amino acid preparations, anti-tussives, anti-uricemic drugs, anti-viral drugs, anabolic preparations, systemic and non-systemic anti-infective agents, anti-neoplastics, anti-parkinsonian agents, anti-rheumatic agents, appetite stimulants, biological response modifiers, blood modifiers, bone metabolism regulators, cardiovascular agents, cholinesterase inhibitors, contraceptives, decongestants, dietary supplements, dopamine receptor agonists, endometriosis management agents, enzymes, erectile dysfunction therapies, fertility agents, gastrointestinal agents, homeopathic remedies, hormones, hypercalcemia and hypocalcemia management agents, immunomodulators, immunosuppressives, migraine preparations, motion sickness treatments, muscle relaxants, obesity management agents, osteoporosis preparations, oxytocics, parasympatholytics, parasympathomimetics, prostaglandins, psychotherapeutic agents, respiratory agents, sedatives, smoking cessation aids, sympatholytics, tremor preparations, urinary tract agents, vasodilators, laxatives, antacids, ion exchange resins, anti-pyretics, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances, coronary dilators, cerebral dilators, peripheral vasodilators, psycho-tropics, stimulants, anti-hypertensive drugs, vasoconstrictors, migraine treatments, antibiotics, tranquilizers, anti-psychotics, anti-tumor drugs, anti-coagulants, anti-thrombotic drugs, hypnotics, anti-emetics, anti-nauseants, anti-convulsants, neuromuscular drugs, hyper- and hypo-glycemic agents, thyroid and anti-thyroid preparations, diuretics, anti-spasmodics, terine relaxants, anti-obesity drugs, erythropoietic drugs, anti-asthmatics, cough suppressants, mucolytics, DNA and genetic modifying drugs, and combinations thereof. 
     
     
         4 . The drug delivery composition of  claim 1 , further including a material comprising amorphous silicon dioxide. 
     
     
         5 . The drug delivery composition of  claim 1 , wherein the flavor is peppermint oil. 
     
     
         6 . The drug delivery composition of  claim 1 , wherein said taste-masking agent is a thin film coating over portions of said active. 
     
     
         7 . The drug delivery composition of  claim 1 , wherein the taste-masking agent is a water-soluble polymer. 
     
     
         8 . The drug delivery composition of  claim 7 , wherein said water-soluble polymer has an average molecular weight of equal to or greater than about 40,000. 
     
     
         9 . The drug delivery composition of  claim 1 , wherein the taste-masking agent is selected from the group consisting of acrylic polymers, cellulosic polymers, vinyl polymers, crown ethers, hydrogenated oils and waxes, and combinations thereof. 
     
     
         10 . The drug delivery composition of  claim 1 , wherein said variation of drug content is less than 5% by weight per film dosage unit. 
     
     
         11 . A drug delivery composition for making individual dosage units in a self-supporting film dosage form, which individual unit doses contain a desired amount of at least one active, the composition comprising:
 (i) a cast film comprising a flowable water-soluble or water swellable film-forming matrix comprising one or more substantially water soluble or water swellable polymers; and at least one active; wherein said matrix has a viscosity sufficient to aid in substantially maintaining non-self-aggregating uniformity of the active in the matrix while forming the self-supporting cast film;   (ii) a particulate active substantially uniformly stationed in the matrix; and   (iii) a taste-masking agent coated or intimately associated with said particulate to provide taste-masking of the active;   wherein the combined particulate and taste-masking agent have a particle size of 200 microns or less and said flowable water-soluble or water swellable film-forming matrix forms a self-supporting film without loss of substantial uniformity in the stationing of said particulate active therein; and   wherein the uniformity in the stationing of the active in the matrix is measured by substantially equally sized individual unit doses which do not vary by more than 10% of said desired amount of said at least one active.   
     
     
         12 . The drug delivery composition of  claim 11 , wherein the active is selected the group consisting of opiates, opiate derivatives, analgesics, apomorphine, hormones, tadalafil, urinary tract agents, migraine treatments, alprazolam, biological response modifiers, and combinations thereof. 
     
     
         13 . The drug delivery composition of  claim 11 , wherein said active is selected from the group consisting of anxiolytics, central nervous system stimulants, ace-inhibitors, antianginal drugs, anti-arrhythmias, anti-asthmatics, anti-cholesterolemics, anesthetics, anti-convulsants, anti-depressants, anti-diabetic agents, anti-diarrhea preparations, antidotes, anti-histamines, anti-hypertensive drugs, anti-inflammatory agents, anti-lipid agents, anti-manics, anti-nauseants, anti-stroke agents, anti-thyroid preparations, anti-tumor drugs, anti-viral agents, acne drugs, alkaloids, amino acid preparations, anti-tussives, anti-uricemic drugs, anti-viral drugs, anabolic preparations, systemic and non-systemic anti-infective agents, anti-neoplastics, anti-parkinsonian agents, anti-rheumatic agents, appetite stimulants, biological response modifiers, blood modifiers, bone metabolism regulators, cardiovascular agents, cholinesterase inhibitors, contraceptives, decongestants, dietary supplements, dopamine receptor agonists, endometriosis management agents, enzymes, erectile dysfunction therapies, fertility agents, gastrointestinal agents, homeopathic remedies, hormones, hypercalcemia and hypocalcemia management agents, immunomodulators, immunosuppressives, migraine preparations, motion sickness treatments, muscle relaxants, obesity management agents, osteoporosis preparations, oxytocics, parasympatholytics, parasympathomimetics, prostaglandins, psychotherapeutic agents, respiratory agents, sedatives, smoking cessation aids, sympatholytics, tremor preparations, urinary tract agents, vasodilators, laxatives, antacids, ion exchange resins, anti-pyretics, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances, coronary dilators, cerebral dilators, peripheral vasodilators, psycho-tropics, stimulants, anti-hypertensive drugs, vasoconstrictors, migraine treatments, antibiotics, tranquilizers, anti-psychotics, anti-tumor drugs, anti-coagulants, anti-thrombotic drugs, hypnotics, anti-emetics, anti-nauseants, anti-convulsants, neuromuscular drugs, hyper- and hypo-glycemic agents, thyroid and anti-thyroid preparations, diuretics, anti-spasmodics, terine relaxants, anti-obesity drugs, erythropoietic drugs, anti-asthmatics, cough suppressants, mucolytics, DNA and genetic modifying drugs, and combinations thereof. 
     
     
         14 . The drug delivery composition of  claim 11 , further including a material comprising amorphous silicon dioxide. 
     
     
         15 . The drug delivery composition of  claim 11 , wherein said taste-masking agent is a thin film coating over portions of said active. 
     
     
         16 . The drug delivery composition of  claim 11 , wherein the taste-masking agent is a water-soluble polymer. 
     
     
         17 . The drug delivery composition of  claim 16 , wherein said water-soluble polymer has an average molecular weight of equal to or greater than about 40,000. 
     
     
         18 . The drug delivery composition of  claim 11 , wherein the taste-masking agent is selected from the group consisting of acrylic polymers, cellulosic polymers, vinyl polymers, crown ethers, hydrogenated oils and waxes, and combinations thereof. 
     
     
         19 . The drug delivery composition of  claim 11 , wherein said variation of drug content is less than 5% by weight per film dosage unit. 
     
     
         20 . A drug delivery composition for making individual unit doses, in a self-supporting film dosage form, which individual unit doses contain a desired amount of at least one active, the composition comprising:
 (i) a cast film comprising a flowable water-soluble or water swellable film-forming matrix comprising one or more substantially water soluble or water swellable polymers; and at least one active; wherein said matrix has a viscosity sufficient to aid in substantially maintaining non-self-aggregating uniformity of the active in the matrix while forming the self-supporting cast film;   (ii) a particulate active substantially uniformly stationed in the matrix; and   (iii) a taste-masking agent coated or intimately associated with said particulate to provide taste-masking of the active;   wherein the combined particulate and taste-masking agent have a particle size of 200 microns or less and said flowable water-soluble or water swellable film-forming matrix is capable of being dried by balancing rheological properties of the composition, heating and fluid flow without loss of substantial uniformity in the stationing of said particulate active therein; and   wherein the uniformity of the matrix is measured by substantially equally sized individual unit doses which do not vary by more than 10% of said desired amount of said at least one active.   
     
     
         21 . The drug delivery composition of  claim 20 , wherein the active is selected the group consisting of opiates, opiate derivatives, analgesics, apomorphine, hormones, tadalafil, urinary tract agents, migraine treatments, alprazolam, biological response modifiers, and combinations thereof. 
     
     
         22 . The drug delivery composition of  claim 20 , wherein said active is selected from the group consisting of anxiolytics, central nervous system stimulants, ace-inhibitors, antianginal drugs, anti-arrhythmias, anti-asthmatics, anti-cholesterolemics, anesthetics, anti-convulsants, anti-depressants, anti-diabetic agents, anti-diarrhea preparations, antidotes, anti-histamines, anti-hypertensive drugs, anti-inflammatory agents, anti-lipid agents, anti-manics, anti-nauseants, anti-stroke agents, anti-thyroid preparations, anti-tumor drugs, anti-viral agents, acne drugs, alkaloids, amino acid preparations, anti-tussives, anti-uricemic drugs, anti-viral drugs, anabolic preparations, systemic and non-systemic anti-infective agents, anti-neoplastics, anti-parkinsonian agents, anti-rheumatic agents, appetite stimulants, biological response modifiers, blood modifiers, bone metabolism regulators, cardiovascular agents, cholinesterase inhibitors, contraceptives, decongestants, dietary supplements, dopamine receptor agonists, endometriosis management agents, enzymes, erectile dysfunction therapies, fertility agents, gastrointestinal agents, homeopathic remedies, hormones, hypercalcemia and hypocalcemia management agents, immunomodulators, immunosuppressives, migraine preparations, motion sickness treatments, muscle relaxants, obesity management agents, osteoporosis preparations, oxytocics, parasympatholytics, parasympathomimetics, prostaglandins, psychotherapeutic agents, respiratory agents, sedatives, smoking cessation aids, sympatholytics, tremor preparations, urinary tract agents, vasodilators, laxatives, antacids, ion exchange resins, anti-pyretics, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances, coronary dilators, cerebral dilators, peripheral vasodilators, psycho-tropics, stimulants, anti-hypertensive drugs, vasoconstrictors, migraine treatments, antibiotics, tranquilizers, anti-psychotics, anti-tumor drugs, anti-coagulants, anti-thrombotic drugs, hypnotics, anti-emetics, anti-nauseants, anti-convulsants, neuromuscular drugs, hyper- and hypo-glycemic agents, thyroid and anti-thyroid preparations, diuretics, anti-spasmodics, terine relaxants, anti-obesity drugs, erythropoietic drugs, anti-asthmatics, cough suppressants, mucolytics, DNA and genetic modifying drugs, and combinations thereof. 
     
     
         23 . The drug delivery composition of  claim 20 , further including a material comprising amorphous silicon dioxide. 
     
     
         24 . The drug delivery composition of  claim 20 , wherein water-soluble or water swellable polymers are selected from the group consisting of polyethylene oxide, cellulosic polymers and combinations thereof. 
     
     
         25 . The drug delivery composition of  claim 20 , wherein the taste-masking agent is a thin film coating over portions of said active. 
     
     
         26 . The drug delivery composition of  claim 20 , wherein the taste-masking agent is selected from the group consisting of acrylic polymers, cellulosic polymers, vinyl polymers, crown ethers, hydrogenated oils and waxes, and combinations thereof. 
     
     
         27 . The drug delivery composition of  claim 20 , wherein said variation of drug content is less than 5% by weight per film dosage unit. 
     
     
         28 . A multi-layer film for delivery of a desired amount of at least one pharmaceutical or bioactive active in substantially equal sized individual unit doses, said multi-layer film comprising:
 (a) a first film layer comprising:
 (i) an ingestible, polymer matrix comprising at least one water soluble or water-swellable polymer; and 
   (b) one or more additional film layers comprising:
 (i) an ingestible, polymer matrix comprising at least one water-soluble or water-swellable polymer; and 
   wherein at least one of (a) said first film layer or (b) said one or more additional film layers comprises a matrix that comprises: at least one pharmaceutical or bioactive active, said at least one pharmaceutical or bioactive active being comprised of active components having a particle size of 200 microns or less, said components being substantially uniformly distributed in said matrix;   wherein at least one of said first film layer or said one or more additional film layers further comprises: at least one of a flavor, sweetener, flavor enhancer, or combination thereof;   wherein said first film layer is substantially in contact with at least one of said one or more additional film layers; and   wherein said multi-layer film is self-supporting and said at least one or more pharmaceutical or bioactive active components is substantially uniformly distributed within at least one of said first film layer or said one or more additional film layers, whereby said substantially uniform distribution is such that substantially equal sized individual unit doses of said multi-layer film do not vary by more than 10% from said desired amount of said at least one or more pharmaceutical or bioactive active.   
     
     
         29 . The drug delivery composition of  claim 28 , wherein the active is selected the group consisting of opiates, opiate derivatives, analgesics, apomorphine, hormones, tadalafil, urinary tract agents, migraine treatments, alprazolam, biological response modifiers, and combinations thereof. 
     
     
         30 . The drug delivery composition of  claim 28 , wherein said active is selected from the group consisting of anxiolytics, central nervous system stimulants, ace-inhibitors, antianginal drugs, anti-arrhythmias, anti-asthmatics, anti-cholesterolemics, anesthetics, anti-convulsants, anti-depressants, anti-diabetic agents, anti-diarrhea preparations, antidotes, anti-histamines, anti-hypertensive drugs, anti-inflammatory agents, anti-lipid agents, anti-manics, anti-nauseants, anti-stroke agents, anti-thyroid preparations, anti-tumor drugs, anti-viral agents, acne drugs, alkaloids, amino acid preparations, anti-tussives, anti-uricemic drugs, anti-viral drugs, anabolic preparations, systemic and non-systemic anti-infective agents, anti-neoplastics, anti-parkinsonian agents, anti-rheumatic agents, appetite stimulants, biological response modifiers, blood modifiers, bone metabolism regulators, cardiovascular agents, cholinesterase inhibitors, contraceptives, decongestants, dietary supplements, dopamine receptor agonists, endometriosis management agents, enzymes, erectile dysfunction therapies, fertility agents, gastrointestinal agents, homeopathic remedies, hormones, hypercalcemia and hypocalcemia management agents, immunomodulators, immunosuppressives, migraine preparations, motion sickness treatments, muscle relaxants, obesity management agents, osteoporosis preparations, oxytocics, parasympatholytics, parasympathomimetics, prostaglandins, psychotherapeutic agents, respiratory agents, sedatives, smoking cessation aids, sympatholytics, tremor preparations, urinary tract agents, vasodilators, laxatives, antacids, ion exchange resins, anti-pyretics, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances, coronary dilators, cerebral dilators, peripheral vasodilators, psycho-tropics, stimulants, anti-hypertensive drugs, vasoconstrictors, migraine treatments, antibiotics, tranquilizers, anti-psychotics, anti-tumor drugs, anti-coagulants, anti-thrombotic drugs, hypnotics, anti-emetics, anti-nauseants, anti-convulsants, neuromuscular drugs, hyper- and hypo-glycemic agents, thyroid and anti-thyroid preparations, diuretics, anti-spasmodics, terine relaxants, anti-obesity drugs, erythropoietic drugs, anti-asthmatics, cough suppressants, mucolytics, DNA and genetic modifying drugs, and combinations thereof.