Oral film compositions and dosage forms having precise active dissolution profiles
An oral film in an individual unit dose for delivery of one or more actives is disclosed herein, the film having a precisely calculated and controlled active dissolution profile. A wide variety of actives may be used, including, for example, clobazam, diazepam, or riluzole. Also disclosed are methods of treating a variety of diseases and conditions, for example, epilepsy and seizures, by administering the oral film disclosed herein.
1. A self-supporting oral film for delivery of a desired amount of an active in an individual unit dose, said film comprising:
a) a water-soluble polymer matrix, a water swellable polymer matrix, or a water-soluble and water swellable polymer matrix;
b) the active being clobazam and having an average particle size D90 of less than about 160 microns; and
c) an additive selected from the group consisting of a sweetener, a flavor, a flavor enhancer, a filler, a plasticizer, a dye, a pigment, a permeation enhancer, a buffer, a preservative, silicon dioxide, an anti-tacking agent, and any combination thereof;
wherein, upon placing the film in a medium, about 40% or more of the active is dissolved in the medium after about 5 minutes.
2. The film of claim 1 , wherein the active has an average particle size D90 of less than about 120 microns.
3. The film of claim 1 , wherein the active has an average particle size D50 of less than about 30 microns.
4. The film of claim 2 , wherein the active has an average particle size D10 of less than about 10 microns.
5. The film of claim 1 , wherein, upon placing the film in the medium, more than about 55% of the active is dissolved after about 5 minutes.
6. The film of claim 1 , wherein, upon placing the film in the medium, more than about 5% of the active is dissolved after about 1.5 minutes.
7. The film of claim 1 , wherein the individual unit dose contains about 2 mg to about 20 mg of clobazam.
8. The film of claim 7 , wherein the individual unit dose contains about 5 mg of clobazam.
9. The film of claim 8 , wherein, upon placing the film in the medium, more than about 30% of the active is dissolved after about 1 minute.
10. The film of claim 8 , wherein, upon placing the film in the medium, more than about 70% of the active is dissolved after about 2 minutes.
11. The film of claim 8 , wherein, upon placing the film in the medium, more than about 90% of the active is dissolved after about 2.5 minutes.
12. The film of claim 7 , wherein the individual unit dose contains about 10 mg of clobazam.
13. The film of claim 12 , wherein, upon placing the film in the medium, more than about 50% of the active is dissolved after about 1.5 minutes.
14. The film of claim 12 , wherein, upon placing the film in the medium, more than about 70% of the active is dissolved after about 2.5 minutes.
15. The film of claim 7 , wherein the individual unit dose contains about 20 mg of clobazam.
16. The film of claim 15 , wherein, upon placing the film in the medium, more than about 2% of the active is dissolved after about 1.5 minutes.
17. The film of claim 15 , wherein, upon placing the film in the medium, more than about 40% of the active is dissolved after about 3.5 minutes.
18. A method of treating epilepsy and/or seizures in a human comprising administering to said human the oral film individual unit dose of claim 1 .
19. The film of claim 1 , wherein, upon placing the film in the medium about 20% or more of the active is dissolved in the medium after about 3 minutes.
20. The film of claim 1 , wherein the water-soluble polymer matrix, the water swellable polymer matrix, or the water-soluble and water swellable polymer matrix comprise a polymer selected from polyethylene oxide (PEO), pullulan, hydroxypropylmethyl cellulose (HPMC), hydroxyethyl cellulose (HPC), hydroxypropyl cellulose, polyvinyl pyrrolidone, carboxymethyl cellulose, polyethylene glycol, xanthan gum, tragancanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methyl-methacrylate copolymer, carboxyvinyl copolymers, starch, gelatin, and combinations thereof.
21. The film of claim 20 , wherein the polymer is polyethylene oxide (PEO).
22. The film of claim 21 , wherein the polyethylene oxide has a molecular weight of at least about 100,000.
23. The film of claim 21 , wherein the polyethylene oxide has a molecular weight from about 100,000 to 300,000.
24. The film of claim 1 , wherein the active has an average particle size D90 of about 8 microns to no more than about 160 microns.