Details for Patent: 9,682,037

Title:	Non-mucoadhesive film dosage forms
Abstract:	Orally disintegrating film dosage forms for delivering active pharmaceutical agents, methods of formulating the dosage forms to retard absorption through the oral mucosa, and methods of using the dosage forms for the treatment of various medical conditions are provided.
Inventor(s):	Leichs; Christian (Burscheid, DE), Breitenbach; Armin (Leverkusen, DE), Lehrke; Ingo (Cologne, DE), Galfetti; Paolo (It, IT)
Assignee:	APR APPLIED PHARMA RESEARCH SA (Balerna, CH)
Filing Date:	Oct 11, 2013
Application Number:	14/052,034
Claims:	1. A non-mucoadhesive orally disintegrating film, able to disintegrate upon contact with saliva in the buccal cavity within about sixty seconds, comprising olanzapine or a pharmaceutically acceptable salt thereof in combination with a hydrophilic binder and a water-soluble diluent, wherein: a) said film comprises from about 5 to about 20 mg olanzapine or a pharmaceutically acceptable salt thereof; b) said olanzapine or pharmaceutically acceptable salt thereof is present in an amount of from about 0.05% to about 50% (w/w/), based on the total weight of the film; c) said film has a Tmax of approximately 6 hours; d) said olanzapine or pharmaceutically acceptable salt thereof has an absolute bioavailability in said film of about 60%; and e) wherein the said film further comprises means for retarding absorption of active ingredient through the oral mucosa wherein the means for retarding the absorption of active ingredient through the oral mucosa are selected from the group consisting of: (1) an ion exchange resin that binds olanzapine and prevents its ionization and dissolution upon disintegration of the film, wherein said ion exchange resin is selected from the group consisting of polymers and copolymers of acrylic acid, methacrylic acid, sulfonated styrene, sulfonated divinylbenzene, dextrans, and silica gel modified by the addition of ionic groups; (2) pH adjusting agents; (3) cyclodextrin or acrylate polymers; and (4) olanzapine in base form; wherein said retarding means are able to deliver greater than 60% of said olanzapine to the gastrointestinal tract when the film is placed on the tongue, allowed to disintegrate and subsequently swallowed. 2. A non-mucoadhesive orally disintegrating film, able to disintegrate upon contact with saliva in the buccal cavity within about sixty seconds, comprising rizatriptan or a pharmaceutically acceptable salt thereof in combination with a hydrophilic binder and a water-soluble diluent, wherein: a) said film comprises from about 2.5 to 15 mg rizatriptan or a pharmaceutically acceptable salt thereof; b) said rizatriptan or pharmaceutically acceptable salt thereof is present in an amount of from about 0.05% to about 50% (w/w/), based on the total weight of the film; c) said film has a Tmax of from about 0.5 to about 3.0 hours; and d) wherein the said film further comprises means for retarding absorption of active ingredient through the oral mucosa wherein the means for retarding the absorption of active ingredient through the oral mucosa are selected from the group consisting of: (1) an ion exchange resin that binds rizatriptan and prevents its ionization and dissolution upon disintegration of the film, wherein said ion exchange resin is selected from the group consisting of polymers and copolymers of acrylic acid, methacrylic acid, sulfonated styrene, sulfonated divinylbenzene, dextrans, and silica gel modified by the addition of ionic groups; (2) pH adjusting agents; (3) cyclodextrin or acrylate polymers; and (4) rizatriptan in base form; wherein said retarding means are able to deliver greater than 60% of said rizatriptan to the gastrointestinal tract when the film is placed on the tongue, allowed to disintegrate and subsequently swallowed. 3. A non-mucoadhesive orally disintegrating film, able to disintegrate upon contact with saliva in the buccal cavity within about sixty seconds, comprising zolmitriptan or a pharmaceutically acceptable salt thereof in combination with a hydrophilic binder and a water-soluble diluent, wherein: a) said film comprises from about 1.5 to 7.5 mg zolmitriptan or a pharmaceutically acceptable salt thereof; b) said zolmitriptan or pharmaceutically acceptable salt thereof is present in an amount of from about 0.05% to about 50% (w/w/), based on the total weight of the film; c) said film has a Tmax of from about 1.0 to about 4.0 hours; and d) wherein the said film further comprises means for retarding absorption of active ingredient through the oral mucosa wherein the means for retarding the absorption of active ingredient through the oral mucosa are selected from the group consisting of: (1) an ion exchange resin that binds zolmitriptan and prevents its ionization and dissolution upon disintegration of the film, wherein said ion exchange resin is selected from the group consisting of polymers and copolymers of acrylic acid, methacrylic acid, sulfonated styrene, sulfonated divinylbenzene, dextrans, and silica gel modified by the addition of ionic groups; (2) pH adjusting agents; (3) cyclodextrin or acrylate polymers; and (4) zolmitriptan in base form; wherein said retarding means are able to deliver greater than 60% of said zolmitriptan to the gastrointestinal tract when the film is placed on the tongue, allowed to disintegrate and subsequently swallowed. 4. The non-mucoadhesive orally disintegrating film of claim 1, wherein said retarding means are able to deliver greater than 80% of said olanzapine to the gastrointestinal tract when the film is placed on the tongue, allowed to disintegrate, and subsequently swallowed. 5. The non-mucoadhesive orally disintegrating film of claim 1, wherein said retarding means are able to deliver greater than 95% of said olanzapine to the gastrointestinal tract when the film is placed on the tongue, allowed to disintegrate, and subsequently swallowed. 6. The non-mucoadhesive orally disintegrating film of claim 1, wherein the film is a single layer homogenous film, having a weight from about 40 to about 120 milligrams, a thickness of from 10 to 200 microns, and a surface area of less than 7 cm2. 7. The non-mucoadhesive orally disintegrating film of claim 2, wherein said retarding means are able to deliver greater than 80% of said rizatriptan to the gastrointestinal tract when the film is placed on the tongue, allowed to disintegrate, and subsequently swallowed. 8. The non-mucoadhesive orally disintegrating film of claim 2, wherein said retarding means are able to deliver greater than 95% of said rizatriptan to the gastrointestinal tract when the film is placed on the tongue, allowed to disintegrate, and subsequently swallowed. 9. The non-mucoadhesive orally disintegrating film of claim 2, wherein the film is a single layer homogenous film, having a weight from about 40 to about 120 milligrams, a thickness of from 10 to 200 microns, and a surface area of less than 7 cm2. 10. The non-mucoadhesive orally disintegrating film of claim 3, wherein said retarding means are able to deliver greater than 80% of said rizatriptan to the gastrointestinal tract when the film is placed on the tongue, allowed to disintegrate, and subsequently swallowed. 11. The non-mucoadhesive orally disintegrating film of claim 3, wherein said retarding means are able to deliver greater than 95% of said rizatriptan to the gastrointestinal tract when the film is placed on the tongue, allowed to disintegrate, and subsequently swallowed. 12. The non-mucoadhesive orally disintegrating film of claim 3, wherein the film is a single layer homogenous film, having a weight from about 40 to about 120 milligrams, a thickness of from 10 to 200 microns, and a surface area of less than 7 cm.sup.2.