Polymer-Based Films and Drug Delivery Systems Made Therefrom

Abstract

The invention relates to the film products and methods of their preparation that demonstrate a non-self-aggregating uniform heterogeneity. Desirably, the films disintegrate in water and may be formed by a controlled drying process, or other process that maintains the required uniformity of the film. The films contain a polymer component which includes polyethylene oxide, optionally blended with at least one additional polymer. The films may alternatively contain a polymer component which includes polyvinyl alcohol, optionally blended with at least one additional polymer. The films also may contain a pharmaceutical and/or cosmetic active agent.

1 . A dissolvable film product comprising: 
 a polymer comprising polyethylene oxide alone or in combination with at least one additional polymeric component,    wherein said film product is free of added plasticizers.    
     
     
         2 . A film product according to  claim 1 , wherein said polyethylene oxide is present in an amount of at least about 20% by weight of said polymer.  
     
     
         3 . A film product according to  claim 1 , wherein said polyethylene oxide is present in an amount up to about 100% by weight of said polymer.  
     
     
         4 . A film product according to  claim 1 , wherein said at least one additional polymeric component is present in an amount up to about 80% by weight of said polymer.  
     
     
         5 . A film product according to  claim 1 , wherein said at least one additional polymeric component is selected from the group consisting of polyvinyl alcohol, hydroxypropyl methylcellulose, pectin, polydextrose, hydroxypropyl cellulose, sodium alginate, pullulan, carrageenan, polyvinyl pyrrolidone, starch, propylene glycol alginate, poloxamer, copolymers of acrylic acid and alkyl acrylate, xanthan, or combinations thereof.  
     
     
         6 . A film product according to  claim 1 , wherein said at least one additional polymeric component is polyvinyl alcohol.  
     
     
         7 . A film product according to  claim 1 , wherein said polyethylene oxide has a molecular weight of about 100,000 to about 900,000.  
     
     
         8 . A film product according to  claim 1 , wherein said polyethylene oxide has a molecular weight of about 100,000 to about 4 million.  
     
     
         9 . A film product according to  claim 1 , wherein said polyethylene oxide has a molecular weight of about 100,000 to about 300,000 in combination with polyethylene oxide having a molecular weight of about 600,000 to about 900,000.  
     
     
         10 . A film product according to  claim 1 , further comprising an active component selected from the group consisting of cosmetic agents, pharmaceutical agents, bioactive agents, and combinations thereof.  
     
     
         11 . A film product according to  claim 10 , wherein said bioactive agents are selected from the group consisting of enzymes, antigens, and allergens.  
     
     
         12 . A film product according to  claim 10 , wherein said active component is selected from the group consisting of ace-inhibitors, anti-anginal drugs, anti-arrhythmias, anti-asthmatics, anti-cholesterolemics, analgesics, 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, central nervous system stimulates, 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, psychotropics, 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.  
     
     
         13 . A film product according to  claim 1 , further comprising a densifying agent.  
     
     
         14 . A film product according to  claim 13 , wherein said densifying agent is simethicone.  
     
     
         15 . A film product according to  claim 1 , further comprising a solubility enhancing agent.  
     
     
         16 . A film product according to  claim 1 , wherein said film is resistant to tearing when dried.  
     
     
         17 . A film product according to  claim 1 , wherein said film is flexible when dried.  
     
     
         18 . A film product according to  claim 1 , wherein polymer comprises polyethylene oxide in amounts sufficient to promote adhesion to mucosal tissue.  
     
     
         19 . A dissolvable film product comprising a polymer, said polymer comprising polyvinyl alcohol alone or in combination with at least one additional polymeric component.  
     
     
         20 . A film product according to  claim 19 , wherein said film product is free of added plasticizers.  
     
     
         21 . A film product according to  claim 19 , wherein said at least one additional polymeric component is selected from the group consisting of a cellulosic polymer, polyvinyl pyrrolidone, polyethylene oxide, an alginate, a pectin, or a combination thereof.  
     
     
         22 . A film product according to  claim 19 , wherein said at least one additional polymeric component is polyethylene oxide.  
     
     
         23 . A film product according to  claim 19 , wherein the polyvinyl alcohol is present in an amount of about 0.5% to about 80% by weight of the film product.  
     
     
         24 . A film product according to  claim 19 , wherein the polyvinyl alcohol is present in an amount of about 1% to about 50% by weight of the film product.  
     
     
         25 . A film product according  claim 19 , wherein the polyvinyl alcohol is present in an amount of about 5% to about 25% by weight of the film product.  
     
     
         26 . A film product according to  claim 19 , wherein said bioactive agents are selected from the group consisting of enzymes, antigens, and allergens.  
     
     
         27 . A film product according to  claim 19 , wherein said active component is selected from the group consisting of ace-inhibitors, anti-anginal drugs, anti-arrhythmias, anti-asthmatics, anti-cholesterolemics, analgesics, 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, antiviral 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, central nervous system stimulates, 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, antipyretics, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances, coronary dilators, cerebral dilators, peripheral vasodilators, psychotropics, 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.  
     
     
         28 . A water-soluble film product comprising: 
 a polymer comprising about 20% to about 100% by weight polyethylene oxide, about 0% to about 80% by weight of at least one additional polymeric component;    an active component;    sucralose;    precipitated calcium carbonate;    at least one flavoring;    simethicone;    water; and    at least one colorant,    wherein said film product is free of added plasticizers.    
     
     
         29 . A film product according to  claim 28 , wherein said at least one additional polymeric component is selected from the group consisting of polyvinyl alcohol, hydroxypropyl methylcellulose, pectin, polydextrose, hydroxypropyl cellulose, sodium alginate, pullulan, carrageenan, polyvinyl pyrrolidone, starch, propylene glycol alginate, poloxamer, copolymers of acrylic acid and alkyl acrylate, xanthan, or combinations thereof.  
     
     
         30 . A water soluble film product comprising: 
 a) at least one water-soluble polymer comprising: 
 i) about .5% to 80% by weight polyvinyl alcohol; and  
 ii) about 0% to 95% by weight at least one additional polymeric component;  
   b) an active component;    c) sweetener; and    d) at least one flavoring agent.    
     
     
         31 . A film product according to  claim 30 , wherein said at least one additional polymeric component is selected from the group consisting of a cellulosic polymer, starch, polyvinyl pyrrolidone, polyethylene oxide, an alginate, a pectin, or a combination thereof.  
     
     
         32 . A film product according to  claim 30 , wherein said at least one additional polymeric component is polyethylene oxide.  
     
     
         33 . An edible water-soluble delivery system in the form of a film composition, comprising: 
 at least one water-soluble polymer comprising polyethylene oxide alone or in combination with at least one additional polymeric component,    wherein said film product is free of added plasticizers.    
     
     
         34 . An edible water-soluble delivery system according to  claim 33 , wherein said at least one additional polymeric component is selected from the group consisting of polyvinyl alcohol, hydroxypropyl methylcellulose, pectin, polydextrose, hydroxypropyl cellulose, sodium alginate, pullulan, carrageenan, polyvinyl pyrrolidone, starch, propylene glycol alginate, poloxamer, copolymers of acrylic acid and alkyl acrylate, xanthan, or combinations thereof.  
     
     
         35 . An edible water-soluble delivery system according to  claim 33 , further comprising an active component selected from the group consisting of cosmetic agents, pharmaceutical agents, bioactive agents, and combinations thereof.  
     
     
         36 . An edible water-soluble delivery system in the form of a film composition, comprising: 
 at least one water-soluble polymer comprising polyvinyl alcohol alone or in combination with at least one additional polymeric component.    
     
     
         37 . A delivery system according to  claim 36 , wherein said film composition is free of added plasticizers.  
     
     
         38 . An edible water-soluble delivery system according to  claim 36 , wherein said at least one additional polymeric component is selected from the group consisting of a cellulosic polymer, starch, polyvinyl pyrrolidone, polyethylene oxide, an alginate, a pectin, or a combination thereof.  
     
     
         39 . An edible water-soluble delivery system according to  claim 36 , further comprising an active component selected from the group consisting of cosmetic agents, pharmaceutical agents, bioactive agents, and combinations thereof.  
     
     
         40 . A process for making a film having a substantially uniform distribution of components, comprising the steps of: 
 (a) combining at least one water-soluble polymer comprising polyethylene oxide alone or in combination with at least one additional polymeric component, a solvent, and an active component to form a matrix with a uniform distribution of said components;    (b) forming a film from said matrix; and    (c) drying said film,    wherein said film is free of added plasticizers.    
     
     
         41 . A process according to  claim 40 , wherein the step of forming a film from said matrix further comprises casting said matrix onto a surface having top and bottom sides.  
     
     
         42 . A process according to  claim 40 , wherein the step of drying said film further comprises applying heat to said bottom side of said surface.  
     
     
         43 . A process for making a film having a substantially uniform distribution of components, comprising the steps of: 
 (a) combining at least one water-soluble polymer comprising polyvinyl alcohol alone or in combination with at least one additional polymeric component, a solvent, and an active component to form a matrix with a uniform distribution of said components;    (b) forming a film from said matrix; and    (c) drying said film.    
     
     
         44 . A process according to  claim 43 , wherein said film is free of added plasticizers.  
     
     
         45 . A process according to  claim 43 , wherein the step of forming a film from said matrix further comprises casting said matrix onto a surface having top and bottom sides.  
     
     
         46 . A process according to  claim 43 , wherein the step of drying said film further comprises applying heat to said bottom side of said surface.  
     
     
         47 . A process for making a film having a substantially uniform distribution of components, comprising the steps of: 
 (a) combining at least one water-soluble polymer comprising polyethylene oxide alone or in combination with at least one additional polymeric component, and an active component to form a matrix with a uniform distribution of said components; and    (b) extruding said matrix to form a film.    
     
     
         48 . A process according to  claim 47 , further comprising the step of cooling said extruded film.  
     
     
         49 . A process for making a film having a substantially uniform distribution of components, comprising the steps of: 
 (a) combining at least one water-soluble polymer comprising polyvinyl alcohol alone or in combination with at least one additional polymeric component, and an active component to form a matrix with a uniform distribution of said components; and    (b) extruding said matrix to form a film.    
     
     
         50 . A process according to  claim 49 , wherein said film is free of added plasticizers.  
     
     
         51 . A process according to  claim 49 , further comprising the step of cooling said extruded film.  
     
     
         52 . An edible flexible film product being formed by the steps of: 
 (a) combining at least one water-soluble polymer comprising polyethylene oxide alone or in combination with at least one additional polymeric component, a solvent, and an active component to form a matrix with a uniform distribution of said components;    (b) forming a film from said matrix; and    (c) drying said film,    wherein said film is free of added plasticizers.    
     
     
         53 . An edible flexible film product being formed by the steps of: 
 (a) combining at least one water-soluble polymer comprising polyvinyl alcohol alone or in combination with at least one additional polymeric component, a solvent, and an active component to form a matrix with a uniform distribution of said components;    (b) forming a film from said matrix; and    (c) drying said film.    
     
     
         54 . A film product according to  claim 53 , wherein said film is free of added plasticizers.  
     
     
         55 . A method of sublingually administering an active component to a mammal, said method comprising: 
 (a) providing a dissolvable film product, said film product comprising 
 i) a polymer comprising polyethylene oxide alone or in combination with at least one additional polymeric component, wherein said film product is free of added plasticizers; and  
 ii) said active component; and  
   (b) placing the film in a sublingual region of the mammal.    
     
     
         56 . A method according to  claim 55 , wherein said film comprises more than one layer.  
     
     
         57 . A method according to  claim 56 , wherein said active is located in only one layer.  
     
     
         58 . A method of sublingually administering an active component to a mammal, said method comprising: 
 (a) providing a dissolvable film product, said film product comprising 
 i) a polymer comprising polyvinyl alcohol alone or in combination with at least one additional polymeric component; and  
 ii) said active component; and  
   (b) placing the film in a sublingual region of the mammal.    
     
     
         59 . A method according to  claim 58 , wherein said film comprises more than one layer  
     
     
         60 . A method according to  claim 59 , wherein said active is located in only one layer.  
     
     
         61 . A method according to  claim 47 , wherein said film is free of added plasticizers.