Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom

• US 8,685,437 B2
• Filed: 03/26/2009
• Issued: 04/01/2014
• Est. Priority Date: 10/12/2001
• Status: Expired due to Term

• Current Assignee: Aquestive Therapeutics, Inc.
• Original Assignee: Monosol Rx LLC (Kuraray Company Limited)
• Inventors: Yang, Robert K., Fuisz, Richard C., Myers, Garry L., Fuisz, Joseph M.
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): CRAIGO, WILLIAM A
• Application Number:
  US12/411,505
• Publication Number:
  US 20090181069A1
• Time in Patent Office: 1,832 Days
• Field of Search: 424/439, 427/2.31
• US Class Current: 424/439
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/422 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/435 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 31/4525 containing a five-membered ring with oxygen as a ring hetero atom
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/80 Polymers containing hetero atoms not provided for in groups A61K31/755 - A61K31/795
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• 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 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 47/46 Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
• 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 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• 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: A61K 9/7015 Drug-containing film-forming compositions, e.g. spray-on
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 : for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/10 : Expectorants
• CPC Class Codes: A61P 11/14 : Antitussive agents
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C08J 5/18 : Manufacture of films or sheets

Abstract

The invention relates to the film products and methods of their preparation that demonstrate a non-self-aggregating uniform heterogeneity. 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.

Claims

1. A process for forming a self-supporting, edible film having a substantially uniform distribution of components comprising at least one anti-emetic compound, said film being dissolvable or disintegrable, comprising the steps of:

(a) providing a wet matrix having a uniform distribution of edible components, said components comprising a water-soluble polymer component, an active component comprising at least one anti-emetic compound in the form of particles and water to form an edible matrix with a compositionally uniform distribution of said components;

(b) deaerating said matrix by mixing to prevent cavitation of the matrix in a manner which pulls air into the matrix;

(c) forming a wet film from said deaerated wet matrix by coating or casting the film;

(d) drying said film within about 10 minutes or fewer,

wherein said drying step further comprises;

(i) rapidly forming a visco-elastic film having said anti-emetic particles uniformly distributed throughout within about the first 4.0 minutes by applying hot air currents at temperatures of about 60°

C. to about 100°

C. to said film to prevent flow migration and intermolecular forces from creating aggregates or conglomerates of said anti-emetic particles thereby maintaining the compositional uniform distribution of components; and

(ii) further drying said visco-elastic film to form a self-supporting edible film having anti-emetic particles uniformly distributed throughout; and

(e) dividing said self-supporting film into dosage forms of substantially equal dimensions, wherein each of said dosage forms is compositionally equal, and wherein said dosage forms are each dissolvable or disintegrable in liquid.

2. The process of claim 1, wherein each of said dosage forms has substantially the same mass.

3. The process of claim 1, wherein each of said dosage forms has substantially the same thickness.

5. The process of claim 1, wherein said at least one anti-emetic compound is granisetron.

6. The process of claim 1, wherein said at least one anti-emetic compound is nabilone.

4. A process for forming a self-supporting, edible film having a substantially uniform distribution of components comprising at least one anti-emetic compound, said film being dissolvable or disintegrable, comprising the steps of:

(a) providing a wet matrix having a uniform distribution of edible components, said components comprising a water-soluble polymer component, an active component comprising at least one anti-emetic compound in the form of particles and water to form an edible matrix with a compositionally uniform distribution of said components;

(b) deaerating said matrix by mixing to prevent cavitation of the matrix, thereby reducing formation of air bubbles;

(c) forming a wet film from said deaerated wet matrix by coating or casting the film, said film having a top surface, a bottom surface and a depth between said top and bottom surfaces; and

(d) drying said film within about 10 minutes or fewer,

wherein said drying step further comprises;

(i) rapidly forming a visco-elastic film having said anti-emetic particles uniformly distributed throughout within about the first 4.0 minutes by applying hot air currents at temperatures of about 60°

C. to about 100°

C. to said film to prevent flow migration and intermolecular forces from creating aggregates or conglomerates of said anti-emetic particles thereby maintaining the compositional uniform distribution of components; and

(ii) further drying said visco-elastic film to form a self-supporting edible film having anti-emetic particles uniformly distributed throughout, said dried film having a uniform distribution of said polymer and said solvent components, a uniform weight and a uniform thickness, and wherein said dried film is dissolvable or disintegrable in liquid.

7. The process of claim 4, wherein said at least one anti-emetic compound is granisetron.

8. The process of claim 4, wherein said at least one anti-emetic compound is nabilone.