Claims for Patent: 10,888,499

Summary for Patent: 10,888,499

Title:	Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom
Abstract:	The invention relates to film products containing desired levels of active components and methods of their preparation. 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. Desirably, the films may be exposed to temperatures above that at which the active components typically degrade without concern for loss of the desired activity.
Inventor(s):	Yang; Robert K. (Henderson, NV), Fuisz; Richard C. (Beverly Hills, CA), Myers; Garry L. (Kingsport, TN), Fuisz; Joseph M. (Surfside, FL)
Assignee:	Aquestive Therapeutics, Inc. (Warren, NJ)
Application Number:	16/505,327
Patent Claims:	1. A process for manufacturing a resulting pharmaceutical film suitable for commercialization and regulatory approval said resulting pharmaceutical film having a substantially uniform distribution of a desired amount of a pharmaceutical active in individual doses of the resulting pharmaceutical film, comprising the steps of: (a) forming a Non-Newtonian visco-elastic polymer matrix by mixing, said matrix comprising a polymer selected from the group consisting of water-soluble polymers, water-swellable polymers and combinations thereof, a solvent selected from the group consisting of water, a polar organic solvent and combinations thereof, a pharmaceutical active, which polymer matrix is a shear-thinning pseudoplastic fluid when exposed to shear rates of 10-10.sup.5 sec.sup.-1, said polymer matrix having a substantially uniform distribution of said pharmaceutical active; (b) casting said polymer matrix; (c) conveying said polymer matrix through a drying apparatus and rapidly drying said polymer matrix, to remove at least a portion of said solvent from said matrix to form a visco-elastic film having said pharmaceutical active substantially uniformly distributed throughout by rapidly increasing the viscosity of said polymer matrix upon initiation of drying within about the first 4 minutes to maintain said uniform distribution of said pharmaceutical active by locking-in or substantially preventing migration of said pharmaceutical active, wherein the temperature of the polymer matrix is 100.degree. C. or less, wherein said drying apparatus uses air currents, which have forces below a yield value of the polymer matrix during drying, wherein content uniformity of said pharmaceutical active in substantially equal sized individual dosage units of said visco-elastic film is such that the amount of the pharmaceutical active varies by no more than 10% from the desired amount; and (d) forming the resulting pharmaceutical film from said visco-elastic film by further controlling drying through a process comprising drying at a temperature differential ranging from 5.degree. C. to 30.degree. C. between polymer matrix inside temperature and outside exposure temperature to minimize degradation wherein water content of said resulting film is 10% or less, wherein said resulting pharmaceutical film having said substantially uniform distribution of pharmaceutical active by said locking-in or substantially preventing migration of said pharmaceutical active is maintained, such that content uniformity of said pharmaceutical active in substantially equal sized individual dosage units of said resulting pharmaceutical film is such that the amount of the pharmaceutical active varies by no more than 10% from the desired amount. 2. The method of claim 1, wherein the pharmaceutical active is selected from the group consisting of opiates, opiate derivatives, analgesics, biological response modifiers, urinary tract agents, tadalafil, apomorphine, migraine treatments, hormones, alprazolam, anti-nauseants, anti-parkinsonian agents, anti-convulsants, central nervous system drugs, neuromuscular drugs, erectile dysfunction drugs, anti-spasmodics, anti-emetics, drugs for allergies, and combinations thereof. 3. The method of claim 2, wherein the pharmaceutical active is a central nervous system drug. 4. The method of claim 2, wherein the pharmaceutical active is a neuromuscular drug. 5. The method of claim 2, wherein the pharmaceutical active is an anti-parkinsonian agent. 6. The method of claim 2, wherein the pharmaceutical active is apomorphine. 7. The method of claim 2, wherein the pharmaceutical active is an erectile dysfunction drug. 8. The method of claim 2, wherein the pharmaceutical active is tadalafil. 9. The method of claim 2, wherein the pharmaceutical active is an anti-emetic. 10. The method of claim 2, wherein the pharmaceutical active is a hormone. 11. A pharmaceutical film suitable for commercialization and regulatory approval, said pharmaceutical film having a substantially uniform distribution of a desired amount of a pharmaceutical active in individual doses of the resulting pharmaceutical film, said pharmaceutical film comprising: a polymer matrix comprising a polymer selected from the group consisting of water-soluble polymers, water-swellable polymers and combinations thereof, a solvent selected from the group consisting of water, a polar organic solvent and combinations thereof, and a pharmaceutical active, wherein water content of said film is 10% or less, said pharmaceutical film having a substantially uniform distribution of said pharmaceutical active, such that content uniformity of said pharmaceutical active in substantially equal sized individual dosage units of said pharmaceutical film is such that the amount of the pharmaceutical active varies by no more than 10% from the desired amount. 12. The pharmaceutical film of claim 11, wherein the pharmaceutical active is selected from the group consisting of opiates, opiate derivatives, analgesics, biological response modifiers, urinary tract agents, tadalafil, apomorphine, migraine treatments, hormones, alprazolam, anti-nauseants, anti-parkinsonian agents, anti-convulsants, central nervous system drugs, neuromuscular drugs, erectile dysfunction drugs, anti-spasmodics, anti-emetics, drugs for allergies, and combinations thereof. 13. The pharmaceutical film of claim 12, wherein the pharmaceutical active is a central nervous system drug. 14. The pharmaceutical film of claim 12, wherein the pharmaceutical active is a neuromuscular drug. 15. The pharmaceutical film of claim 12, wherein the pharmaceutical active is an anti- parkinsonian agent. 16. The pharmaceutical film of claim 12, wherein the pharmaceutical active is apomorphine. 17. The pharmaceutical film of claim 12, wherein the pharmaceutical active is an erectile dysfunction drug. 18. The pharmaceutical film of claim 12, wherein the pharmaceutical active is tadalafil. 19. The pharmaceutical film of claim 12, wherein the pharmaceutical active is an anti-emetic. 20. The pharmaceutical film of claim 12, wherein the pharmaceutical active is a hormone.