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 . An oral film for delivery of an active in individual unit doses comprising:
 (i) a continuously cast and dried film produced on a manufacturing coating line, from which substantially equally sized individual dosage units containing a desired amount of active are cut, said continuously 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 particulate active substantially uniformly distributed in the film-forming matrix;   wherein said matrix has a viscosity sufficient to aid in substantially maintaining non-self-aggregating uniformity of the particulate active in the matrix; and   (ii) a taste-masking agent coated onto or intimately associated with the particulate active to provide taste-masking of the active;   wherein the combined particulate active and taste-masking agent have a particle size of 200 microns or less and the flowable water-soluble or water swellable film-forming matrix, as continuously cast on the manufacturing coating line, is capable of being dried without loss of substantial uniformity in the distribution of the particulate active therein; and   wherein said uniformity subsequent to continuously casting and drying of the film is measured by the cut substantially equally sized individual unit doses which do not vary by more than 10% of a desired amount of the at least one active.   
     
     
         2 . The oral film of  claim 1 , wherein the particulate active has a particle size of 150 microns or less. 
     
     
         3 . The oral film of  claim 1 , wherein the particulate active has a particle size of 100 microns or less. 
     
     
         4 . The oral film of  claim 1 , wherein said uniformity of active subsequent to continuously casting and drying of the film is measured by the cut substantially equally sized individual unit doses which do not vary by more than 5%. 
     
     
         5 . The oral film of  claim 1 , wherein said taste-masking agent is present in the amount of about 0.1-30% by weight of the oral film. 
     
     
         6 . The oral film of  claim 1 , wherein said taste-masking agent is present in the amount of about 0.01-10% by weight of the oral film. 
     
     
         7 . The oral film of  claim 1 , wherein said active is an opiate or opiate derivative. 
     
     
         8 . The oral film of  claim 1 , wherein said active is selected from the group consisting of an analgesic, biological response modifiers, urinary tract agents, tadalafil, apomorphine, migraine treatments, hormones, anti-convulsants, alprazolam and combinations thereof. 
     
     
         9 . The oral film of  claim 1 , wherein said taste-masking agent is selected from the group consisting of flavors, sweeteners, flavor enhancers, and combinations thereof to provide taste-masking of the particulate active. 
     
     
         10 . The oral film of  claim 1 , wherein said film-forming polymer matrix comprises a polymer selected from the group consisting of cellulose, cellulose derivatives, polyethylene oxide (PEO), pullulan, methylcellulose, hydroxypropylmethyl cellulose (HPMC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose, polyvinyl pyrrolidone, carboxymethyl cellulose, polyvinyl alcohol, polysaccharides, sodium alginate, xanthan gum, tragancanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers, starch, gelatin, and combinations thereof. 
     
     
         11 . An oral film for delivery of an active in individual unit doses comprising:
 (i) a continuously cast and dried film produced on a manufacturing line, from which substantially equally sized individual dosage units are cut, 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 particulate active;   wherein said matrix has a viscosity sufficient to aid in substantially maintaining non-self-aggregating uniformity of the particulate active in the matrix;   (ii) the particulate active being substantially uniformly distributed in the matrix; and   (iii) a taste-masking agent selected from the group consisting of flavors, sweeteners, flavor enhancers, and combinations thereof to provide taste-masking of the particulate active;   wherein the particulate active has a particle size of 200 microns or less and the flowable water-soluble or water swellable film-forming matrix, as continuously cast on the manufacturing line, is capable of being dried without loss of substantial uniformity in the distribution of the particulate active therein; and   wherein said uniformity subsequent to continuously casting and drying of the film is measured by the cut substantially equally sized individual unit doses which do not vary by more than 10% of a desired amount of the at least one active.   
     
     
         12 . The oral film of  claim 11 , wherein the particulate active has a particle size of 150 microns or less. 
     
     
         13 . The oral film of  claim 11 , wherein the particulate active has a particle size of 100 microns or less. 
     
     
         14 . The oral film of  claim 11 , wherein said uniformity of active subsequent to continuously casting and drying of the film is measured by the cut substantially equally sized individual unit doses which do not vary by more than 5%. 
     
     
         15 . The oral film of  claim 11 , wherein said taste-masking agent is present in the amount of about 0.1-30% by weight of the oral film. 
     
     
         16 . The oral film of  claim 11 , wherein said taste-masking agent is present in the amount of about 0.01-10% by weight of the oral film. 
     
     
         17 . The oral film of  claim 11 , wherein said active is an opiate or opiate derivative. 
     
     
         18 . The oral film of  claim 11 , wherein said active is selected from the group consisting of an analgesic, biological response modifiers, urinary tract agents, tadalafil, apomorphine, migraine treatments, hormones, anti-convulsants, alprazolam and combinations thereof. 
     
     
         19 . The oral film of  claim 11 , wherein said flavor is selected from the group consisting of spearmint oil, cinnamon oil, peppermint oil, clove oil, bay oil, thyme oil, cedar leaf oil, oil of nutmeg, oil of sage, oil of bitter almonds, vanilla, chocolate, coffee, cocoa, citrus oils, fruit flavors, fruit essences, cinnamon derivatives, mints, and combinations thereof. 
     
     
         20 . The oral film of  claim 11 , wherein said film-forming matrix comprises a polymer selected from the group consisting of cellulose, cellulose derivatives, polyethylene oxide (PEO), pullulan, methylcellulose, hydroxypropylmethyl cellulose (HPMC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose, polyvinyl pyrrolidone, carboxymethyl cellulose, polyvinyl alcohol, polysaccharides, sodium alginate, xanthan gum, tragancanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers, starch, gelatin, and combinations thereof. 
     
     
         21 . A drug delivery composition comprising:
 (i) a continuously cast and dried film produced on a manufacturing line comprising a flowable water-soluble or water swellable film-forming matrix comprising one or more substantially water soluble or water swellable polymers; and a desired amount of 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;   (ii) a particulate active substantially uniformly stationed in the matrix; and   (iii) a taste-masking agent selected from the group consisting of flavors, sweeteners, flavor enhancers, and combinations thereof to provide taste-masking of the active;   wherein the particulate active has a particle size of 200 microns or less and said flowable water-soluble or water swellable film-forming matrix is capable of being continuously cast and dried on the manufacturing line without loss of substantial uniformity in the stationing of said particulate active therein; and   wherein said uniformity subsequent to continuously casting and drying of the matrix is measured by substantially equally sized individual unit doses cut from the cast and dried film which do not vary by more than 10% of said desired amount of said at least one active   
     
     
         22 . The drug delivery composition of  claim 21 , wherein the particulate active has a particle size of 150 microns or less. 
     
     
         23 . The drug delivery composition of  claim 21 , wherein the particulate active has a particle size of 100 microns or less. 
     
     
         24 . The drug delivery composition of  claim 21 , wherein said uniformity of active subsequently to continuously casting and drying of the matrix is measured by substantially equally sized individual unit doses cut from the cast and dried film which do not vary by more than 5%. 
     
     
         25 . The drug delivery composition of  claim 21 , wherein said taste-masking agent is present in the amount of about 0.1-30% by weight of the drug delivery composition. 
     
     
         26 . The drug delivery composition of  claim 21 , wherein said taste-masking agent is present in the amount of about 0.01-10% by weight of the drug delivery composition. 
     
     
         27 . The drug delivery composition of  claim 21 , wherein said active is an opiate or opiate derivative. 
     
     
         28 . The drug delivery composition of  claim 21 , wherein said active is selected from the group consisting of an analgesic, biological response modifiers, urinary tract agents, tadalafil, apomorphine, migraine treatments, hormones, anti-convulsants, alprazolam and combinations thereof. 
     
     
         29 . The drug delivery composition of  claim 21 , wherein said flavor is selected from the group consisting of spearmint oil, cinnamon oil, peppermint oil, clove oil, bay oil, thyme oil, cedar leaf oil, oil of nutmeg, oil of sage, oil of bitter almonds, vanilla, chocolate, coffee, cocoa, citrus oils, fruit flavors, fruit essences, cinnamon derivatives, mints, and combinations thereof. 
     
     
         30 . The drug delivery composition of  claim 21 , wherein said film-forming matrix comprises a polymer selected from the group consisting of cellulose, cellulose derivatives, polyethylene oxide (PEO), pullulan, methylcellulose, hydroxypropylmethyl cellulose (HPMC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose, polyvinyl pyrrolidone, carboxymethyl cellulose, polyvinyl alcohol, polysaccharides, sodium alginate, xanthan gum, tragancanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers, starch, gelatin, and combinations thereof.