Dual and single layer dosage forms

• US 9,017,718 B2
• Filed: 04/22/2010
• Issued: 04/28/2015
• Est. Priority Date: 05/21/2009
• Status: Active Grant

• Current Assignee: Bionex Pharmaceuticals LLC
• Original Assignee: Bionex Pharmaceuticals LLC
• Inventors: Tan, Hock Seng, Chung, Siew Lian
• Primary Examiner(s): Tran, Susan
• Assistant Examiner(s): WORSHAM, JESSICA N
• Application Number:
  US13/060,325
• Publication Number:
  US 20110280925A1
• Time in Patent Office: 1,832 Days
• Field of Search: None
• US Class Current: 424/443
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61M 35/00 Devices for applying media, e.g. remedies, on the human body devices for handling toiletry or cosmetic substances A45D; absorbent pads, e.g. swabs, A61F13/15
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics

Abstract

Provided is a dual-release, dual-adhesiveness flexible thin film dosage form comprising: a quick-release subfilm comprising an admixture of polymer, which comprises predominantly highly water-soluble polymer(s), and a bioactive agent, the polymers and other components of the quick-release subfilm adapted to provide 20 minutes or less erodibility for the quick-release subfilm; and laminated against the quick-release subfilm, a sustained-release subfilm comprising an admixture of polymer, which comprises predominantly hydrophilic, bioadhesive polymer(s), and a second bioactive agent, which can be the same as the first, the polymers and other components of the sustained-release subfilm adapted to provide erodibility of 1 hour or more and 20 hours or less for the sustained-release subfilm, the dosage form having a thickness of 30 mil or less, and being more adhesive on the sustained-release side.

Claims

1. A dual-release, dual-adhesiveness flexible thin film dosage form comprising:

a mucoadhesive, planar quick-release subfilm comprising an admixture of polymers, which comprises (a) highly water-soluble polymer(s), (b) predominantly hydrophilic, bioadhesive polymer(s) and, uniformly distributed in the quick-release subfilm polymers, (c) a bioactive agent that is nicotine, naltrexone, lobeline or ondansetron, the polymers and other components of the quick-release subfilm adapted to provide 1 minute or more and 20 minutes or less erodibility for the quick-release subfilm; and

laminated against the quick-release subfilm, a mucoadhesive, planar sustained-release subfilm comprising an admixture of polymers, which comprises (i) predominantly hydrophilic, bioadhesive polymer(s), and, uniformly distributed in the sustained-release subfilm polymers, (ii) the bioactive agent, the polymers and other components of the sustained-release subfilm adapted to provide erodibility of 1 hour or more and 20 hours or less for the sustained-release subfilm, wherein both subfilms comprise (1) flavoring agent or agents and sweetener or sweeteners, (2) polyoxyethylenated castor oil derivative or derivatives and (3) di-glyceride or di-glycerides,

the dosage form having a thickness of 30 mil or less, and being more adhesive on the sustained-release side, the dosage form having no additional layers, and wherein the dosage for is individually packaged in a moisture-resistant compartment.

2. The thin film dosage form of claim 1, wherein the highly water-soluble polymers comprise soluble cellulose derivatives, polyvinylpyrrolidone, polyvinyl alcohol, polyethylene oxide, polyvinyl alcohol grafted polyethylene glycol copolymer, or mixtures thereof.

3. The thin film dosage form of claim 2, wherein the highly water-soluble polymers comprise soluble polyethylene oxide, polyvinyl alcohol grafted polyethylene glycol copolymer, or mixtures thereof.

4. The thin film dosage form of claim 1, wherein the predominantly hydrophilic, bioadhesive polymers comprise xanthan gum, carrageenan, pectin, sodium carboxymethylcellulose, alginate, polyacrylic acids, high molecular weight polyethylene oxide, or mixtures thereof.

5. The thin film dosage form of claim 4, wherein the predominantly hydrophilic, bioadhesive polymers comprise polyacrylic acids, high molecular weight polyethylene oxide, or mixtures thereof.

6. The thin film dosage form of claim 1, wherein the polymers and other components of the quick-release subfilm are adapted to provide 15 minutes or less erodibility for the quick-release subfilm.

7. The thin film dosage form of claim 1, wherein the polymers and other components of the sustained-release subfilm are adapted to provide a bioactive agent release period of 2 hours or more and 20 hours or less for the bioactive agent provided by the sustained-release subfilm.

8. A method of delivering a bioactive agent comprising applying the sustained-release subfilm of the thin film dosage form of claim 1 to mucosal tissue.

9. The method of claim 8, wherein the thin film dosage form is applied to mucosal tissue of the mouth.

10. The method of claim 9, wherein the quick-release subfilm of the thin film dosage form is applied to the top of the tongue, and the thin film dosage form is applied by transfer from the tongue to the palate.

11. The method of claim 8, further comprising providing the thin film dosage form so that the quick-release and the sustained release subfilms have distinct colors, applying the quick-release colored subfilm to a transfer intermediate, and then transferring the thin film dosage form to the mucosal tissue.

12. The thin film dosage form of claim 2, wherein the predominantly hydrophilic, bioadhesive polymers comprise xanthan gum, carrageenan, pectin, sodium carboxymethylcellulose, alginate, polyacrylic acids, high molecular weight polyethylene oxide, or mixtures thereof.

13. The thin film dosage form of claim 3, wherein the predominantly hydrophilic, bioadhesive polymers comprise xanthan gum, carrageenan, pectin, sodium carboxymethylcellulose, alginate, polyacrylic acids, high molecular weight polyethylene oxide, or mixtures thereof.

14. The thin film dosage form of claim 1, wherein both subfilms comprise mono-glyceride.

15. The thin film dosage form of claim 1, wherein the bioactive agent is nicotine.

16. The thin film dosage form of claim 1, wherein the bioactive agent is naltrexone.

17. The thin film dosage form of claim 1, wherein the bioactive agent is lobeline.

18. The thin film dosage form of claim 1, wherein the bioactive agent is ondansetron.