Dosage Form for Insertion Into the Mouth

• US 20130059854A1
• Filed: 10/18/2012
• Published: 03/07/2013
• Est. Priority Date: 11/03/2008
• Status: Active Grant

• Current Assignee: NAL Pharmaceuticals Ltd. (Yim Hung Poon)
• Original Assignee: NAL Pharmaceuticals Ltd. (Yim Hung Poon)
• Inventors: Ryoo, Je Phil, Chu, Chun Kwong, Wang, Zheng
• Granted Patent: US 8,771,736 B2
• Time in Patent Office: Days
• US Class Current: 514/243
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• 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 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/4045 Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/421 1,3-Oxazoles, e.g. pemoline, trimethadione
• CPC Class Codes: A61K 31/422 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/465 Nicotine; Derivatives thereof
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/78 of acrylic acid or derivatives thereof
• CPC Class Codes: A61K 38/05 Dipeptides
• CPC Class Codes: A61K 38/06 Tripeptides
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• 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 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/38 : Cellulose; Derivatives thereof
• 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 9/0095 : Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/2018 : Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2027 : obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• 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 1/02 : Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/08 : for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 1/10 : Laxatives
• CPC Class Codes: A61P 11/00 : Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 15/00 : Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/10 : for impotence
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 : Antimigraine agents
• CPC Class Codes: A61P 25/20 : Hypnotics; Sedatives
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 : for treating abuse or dependence
• CPC Class Codes: A61P 25/34 : Tobacco-abuse
• 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 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14

Abstract

Oral dosage forms as a biodegradable, water soluble film for delivering pharmaceutically active agents, particularly anti-migraine agents to patients through insertion into the mouth of patient and methods for administering pharmaceutically active agents to patients by insertion into the mouth to provide selective uptake of said agents through the mucosa and thus avoiding the gastrointestinal tract.

Claims

1. A pharmaceutical composition comprising:

a water soluble matrix comprising an effective amount of a pharmaceutically active agent and an absorption enhancer having an HLB of about 8 to about 16, wherein the active agent is an erectile dysfunction medicament.

2. The pharmaceutical composition of claim 1 wherein the absorption enhancer is one or more sucrose fatty acid esters having a combined HLB of about 8 to about 16.

3. The pharmaceutical composition of claim 1 further comprising a nonionic surfactant wherein the combined nonionic surfactant and sucrose fatty acid ester have a combined HLB of about 8 to about 17.

4. The pharmaceutical composition of claim 3 wherein the nonionic surfactant is at least one or more of polysorbate and sorbitan fatty acid ester.

5. The pharmaceutical composition of claim 3 further comprising a secondary absorption enhancer selected from the group consisting of glycerol, ginger oil, cineole and terpenes.

6. The pharmaceutical composition of claim 4 wherein the polysorbate is selected from the group consisting of polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan monopalmitate, polyoxyethylene (20) sorbitan and Polyoxyethylene (20) sorbitan monooleate.

7. The pharmaceutical composition of claim 4 wherein the sorbitan fatty acid ester is selected from the group consisting of sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan tristearate and sorbitan monooleate.

8. The pharmaceutical composition of claim 1 further comprising a film forming agent selected from pullulan or a polymeric mixture of polyvinyl pyrrolidone and a polymeric alginate.

17. The pharmaceutical composition of claim 1 wherein the pharmaceutical composition dissolves in the oral cavity in about 0.25 minutes to about 15 minutes.

18. The pharmaceutical composition of claim 8 wherein the film forming agent is pullulan.

20. The pharmaceutical composition of claim 8 wherein the ratio of polyvinyl pyrrolidone to polymeric alginate in the polymeric mixture is from about 5:

1 to about 1;

3.

21. The pharmaceutical composition of claim 2 wherein the sucrose fatty acid esters are sucrose fatty acid esters having a monomer content of from about 20 percent to about 80 percent.

22. The pharmaceutical composition of claim 2 wherein the sucrose fatty acid esters are selected from the group consisting of sucrose stearate, sucrose palmitate, sucrose laurate, sucrose behenate, sucrose oleate and sucrose erucate.

23. The pharmaceutical composition of claim 8 wherein the polymeric mixture contains, from about 5% to about 95% by weight of polyvinyl pyrrolidone and from about 5% to about 95% by weight of an polymeric alginate, both of said weights being based on the weight of said polymeric mixture.

24. The pharmaceutical composition of claim 1 wherein the matrix is a film.

27. The pharmaceutical composition of claim 1 further comprising a polymeric mixture of polyvinyl pyrrolidone and a polymeric alginate.

28. The pharmaceutical composition of claim 24 wherein the film when placed in the oral cavity will dissolve in about 0.25 minutes to about 15 minutes.

33. The pharmaceutical composition of claim 24 wherein said film contains one or more absorption enhancers in an amount of from about 0.1% by weight to about 20% by weight of the film.

34. The pharmaceutical composition of claim 24 wherein said film contains one or more absorption enhancers in an amount of from about 0.1% by weight to about 15% by weight of the film.

40. The pharmaceutical composition of claim 4 wherein the polymeric mixture contains from about 5% to about 95% by weight of polyvinyl pyrrolidone and from about 5% to about 95% by weight of an polymeric alginate, both of said weights being based on the weight of said polymeric mixture.

41. The pharmaceutical composition of claim 1 wherein said matrix contains an absorption enhancer or a combination of absorption enhancers in a total amount of from about 0.1% by weight to about 20% by weight by weight of the matrix.

42. The pharmaceutical composition of claim 2 wherein said sucrose fatty acid ester is a C₁₂ to C₂₀ saturated fatty acid ester of sucrose.

43. The pharmaceutical composition of claim 2 wherein said sucrose fatty acid ester is a sucrose stearate.

79. The pharmaceutical composition of claim 1 wherein the erectile dysfunction medicament is selected from the group consisting of sildenafil, tadalafil, varenafil and their pharmaceutically acceptable salts.

80. The pharmaceutical composition of claim 1 wherein the erectile dysfunction medicament is sildenafil or its pharmaceutically acceptable salts.

81. The pharmaceutical composition of claim 1 wherein the erectile dysfunction medicament is tadalafil or its pharmaceutically acceptable salts.

82. The pharmaceutical composition of claim 1 wherein the erectile dysfunction medicament is varenafil or its pharmaceutically acceptable salts.

9-16. -16. (canceled)

19. (canceled)

25-26. -26. (canceled)

29-32. -32. (canceled)

35-39. -39. (canceled)

44-57. -57. (canceled)

61-63. -63. (canceled)

72. (canceled)

73. (canceled)

76-77. -77. (canceled)

78. A method for mitigating erectile dysfunction in a patient comprising administering the oral unit dosage form as a water soluble matrix to the oral mucosal membranes of the mouth of a patient, which matrix contains, dispersed therein, a pharmaceutical agent selected from the group consisting of sildenafil, tadalafil, varenafil or pharmaceutically acceptable salts thereof, said pharmaceutical agent being present in said matrix in an amount effective for combating said erectile dysfunction, said matrix composed of a one or more sucrose fatty acid esters having an HLB of about 8 to 16.

58. The method of claim 78 further comprising a polymeric mixture of polyvinyl pyrrolidone and a polymeric alginate.

59. The method of claim 58 wherein the ratio of polyvinyl pyrrolidone to polymeric alginate in the polymeric mixture is from about 5:

1 to about 1;

3.

60. The method of claim 58 wherein the polymeric mixture contains, from about 5% to about 95% by weight of polyvinyl pyrrolidone and from about 5% to about 95% by weight of an polymeric alginate, both of said weights being based on the weight of said polymeric mixture.

64. The method of claim 78 wherein said matrix is placed under the tongue of said patient.

65. The method of claim 78 wherein said matrix is inserted on the buccal tissue of the mouth of the patient.

66. The method of claim 78 wherein the sucrose fatty acid ester has a monomer content of from about 20 percent to about 80 percent.

67. The method of claim 78 wherein the sucrose fatty acid esters are selected from the group consisting of sucrose stearate, sucrose palmitate, sucrose laurate, sucrose behenate, sucrose oleate and sucrose erucate.

68. The method of claim 78 wherein said fatty acid esters are present in an amount of from about 1% to about 20% based upon the weight of the film.

69. The method of claim 78 further comprising a nonionic surfactant wherein the combined nonionic surfactant and sucrose fatty acid ester have a combined HLB of about 8 to about 17.

70. The method of claim 78 further comprising a secondary absorption enhancer selected from the group consisting of glycerol, tween, span, ginger oil, cineole and terpenes.

71. The method of claim 78 wherein the matrix is a film.

74. The method of claim 78 further comprising pullulan as a film forming agent.

75. The method of claim 78 wherein the active agent is released over a period of time from about 0.25 minutes to about 15 minutes.