US2018000726A1PendingUtilityA1

Sublingual and buccal film compositions

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Assignee: MONOSOL RX LLCPriority: Aug 7, 2009Filed: Sep 8, 2017Published: Jan 4, 2018
Est. expiryAug 7, 2029(~3.1 yrs left)· nominal 20-yr term from priority
Inventors:Garry L. MyersSamuel D. HilbertBill J. BooneB. Arlie BoguePradeep SanghviMadhusudan Hariharan
A61P 25/04A61K 9/006A61K 9/7007A61K 31/485A61K 9/0056A61K 47/10A61K 47/12
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Claims

Abstract

The present invention relates to products and methods for treatment of various symptoms in a patient, including treatment of pain suffered by a patient. The invention more particularly relates to self-supporting dosage forms which provide an active agent while providing sufficient buccal adhesion of the dosage form. Further, the present invention provides a dosage form which is useful in reducing the likelihood of diversion abuse of the active agent.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . Self-supporting, individual film dosage units each containing an agonist and an antagonist, each individual unit comprising:
 (a) about 30 wt % to about 70 wt % of a water-soluble polymeric matrix comprising one or more polyethylene oxide polymers; and a polymer selected from the group consisting of cellulose, a cellulose derivative, polyvinylpyrrolidone (PVP), polyvinylalcohol (PVA), polysaccharides and combinations thereof;   (b) an agonist or a pharmaceutically acceptable salt thereof;   (c) an antagonist or a pharmaceutically acceptable salt thereof; and   (d) a component selected from the group consisting of citral, alphacitral, neral, decanal, a C 8  aldehyde, a C 9  aldehyde, a C 12  aldehyde and combinations thereof;   
       wherein:
 (i) the pKa ratio of agonist:antagonist in the individual dosage units is from about 5.0:9.0 to about 9.5:6.0; 
 (ii) the weight ratio of agonist:antagonist in the oral film is about 6:1 to about 2:1; and 
 (iii) the weight ration of agonist:buffer in the oral film is about 2:1 to about 1:5. 
 
     
     
         2 . The individual film dosage units of  claim 1 , wherein application of the individual dosage units to the oral mucosa results in different absorption of the agonist and the antagonist through the mucosa, with an agonist Cmax of about 0.868 to about 6.94 ng/ml, and an antagonist Cmax of about 32.5 to about 260 pg/ml. (put deleted into spec) 
     
     
         3 . The individual film dosage units  claim 1 , wherein the polymeric matrix further comprises a cellulose selected from the group consisting of hydroxypropylmethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose and combinations thereof. 
     
     
         4 . The individual film dosage units of  claim 1 , further including a material selected from the group consisting of a sugar alcohol, a flavor, an acidulent, a sweetener, a color, a taste-masking agent, a controlled release agent and combinations thereof. 
     
     
         5 . The individual film dosage units of  4 , wherein the sugar alcohol is selected from the group consisting of maltitol, sorbitol, mannitol, xylitol and combinations thereof. 
     
     
         6 . The individual film dosage units of  claim 4 , wherein the acidulent is citric acid. 
     
     
         7 . The individual film dosage units of  claim 4 , wherein the sweetener is selected from the group consisting of acesulfame-K, saccharin, aspartame, sucralose and combinations thereof. 
     
     
         8 . The individual film dosage units of  claim 4 , wherein the flavor is selected from the group consisting of citrus oils, mint oils, and combinations thereof. 
     
     
         9 . The individual film dosage units of  claim 4 , wherein the flavor comprises a lime flavor. 
     
     
         10 . The individual film dosage units of  claim 4 , wherein the color comprises FD&C yellow #6. 
     
     
         11 . The individual film dosage units of  claim 1  further comprising a material selected from the group consisting of stabilizers, preservatives, antioxidants, silicone dioxide and combinations thereof. 
     
     
         12 . The individual film dosage units of  claim 1  wherein the ratio of cellulosic polymer to polyethylene oxide is up to about 4:1. 
     
     
         13 . The individual film dosage units of  claim 1 , wherein the cellulosic polymer is present in amounts up to about 25% by weight of the water soluble polymeric matrix. 
     
     
         14 . The individual film dosage units of  claim 1 , wherein the agonist is selected from the group consisting of sufentanil, morphine, fentanyl, alfentanil, pethidine, apomorphine, alphaprodine, remifentanil, methadone, codeine, dihydrocodeine, oxycodone, oxymorphone, tramadol, combinations thereof, and pharmaceutically acceptable salts thereof. 
     
     
         15 . The individual film dosage units of  claim 1 , wherein antagonist is selected from the group consisting of naloxone, naltrexone, nalorphine, levallorphan, combinations thereof and pharmaceutically acceptable salts thereof. 
     
     
         16 . The individual film dosage units of  claim 1 , wherein the degradation temperature of the agonist and the antagonist is 70° C. or higher. 
     
     
         17 . The individual film dosage units of  claim 4 , wherein the taste-masking agent or controlled release agent is selected from the group consisting of flavors, ion exchange resins, polymer coatings and combinations thereof. 
     
     
         18 . The individual film dosage units of  claim 1  wherein the agonist and the antagonist are in distinct regions of each dosage unit. 
     
     
         19 . A method of treatment comprising administering to a patient one or more of the individual film dosage unit of  claim 1 . 
     
     
         20 . Self-supporting, individual film dosage units each containing an agonist and an antagonist, said individual film dosage units comprising:
 (a) about 30 wt % to about 70 wt % of a water-soluble polymeric matrix comprising one or more polyethylene oxide polymers; and a polymer selected from the group consisting of cellulose, a cellulose derivative, polyvinylpyrrolidone (PVP), polyvinylalcohol (PVA), a polysaccharide and combinations thereof;   (b) an agonist or a pharmaceutically acceptable salt thereof;   (c) an antagonist or a pharmaceutically acceptable salt thereof;   (d) maltitol;   (e) a component selected from the group consisting of citral, alphacitral, neral, decanal, a C 8  aldehyde, a C 9  aldehyde, and a C 12  aldehyde,   (f) acesulfame K;   (g) a color; and   (h) sodium citrate;   
       wherein;
 (i) the pKa ratio of agonist:antagonist in the individual dosage units is from about 5.0:9.0 to about 9.5:6.0; 
 (ii) the weight ratio of agonist:antagonist in the oral film is about 6:1 to about 2:1; and 
 (iii) the weight ratio of agonist:buffer in the oral film is about 2:1 to 1:5. 
 
     
     
         21 . The individual dosage units of  claim 20  wherein application of the individual dosage units to the oral mucosa results in different absorption of the agonist and the antagonist through the mucosa, thus providing an agonist Cmax of about 0.868 to about 6.94 ng/ml and an antagonist Cmax of about 332.5 to about 260 pg/ml. 
     
     
         22 . The oral film of  claim 20 , wherein the agonist is selected from the group consisting of sufentanil, morphine, fentanyl, alfentanil, pethidine, apomorphine, alphaprodine, remifentanil, methadone codeine, dihydrocodeine, oxycodone, oxymorphone, tramadol, combinations thereof, and pharmaceutically acceptable salts thereof. 
     
     
         23 . The oral film of  claim 20 , wherein antagonist is selected from the group consisting of naloxone, naltrexone, nalorphine, levallorphan, combinations thereof and pharmaceutically acceptable salts thereof. 
     
     
         24 . The oral film of  claim 20 , further comprising a material selected from the group consisting of stabilizers, preservatives, antioxidant, silicon dioxide and combinations thereof. 
     
     
         25 . A method of treatment comprising administering to a patient the individual dosage units of  claim 20 . 
     
     
         26 . The oral film of  claim 1  wherein the amount of agonist is from about 2 mg to about 16 mg. 
     
     
         27 . The oral film of  claim 1  wherein the amount of antagonist is from about 0.5 mg to about 4.0 mg. 
     
     
         28 . The oral film of  claim 20 , wherein the amount of agonist is from about 2 mg to about 16 mg. 
     
     
         29 . The oral film of  claim 20 , wherein the amount of antagonist is from about 0.5 mg to about 4.0 mg. 
     
     
         30 . The individual film dosage units of  claim 1  containing less than about 10% by weight solvent per individual dosage units.

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