# US 8,771,736 B2 · Dosage form for insertion into the mouth

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- Number: US 8,771,736 B2
- Document ID: US8771736B2
- Status: Granted
- Kind: B2
- Application number: 13/655,194
- Filed: 2012-10-18
- Published: 2013-03-07
- Granted: 2014-07-08
- Earliest claimed: 2008-11-03
- Assignees: NAL Pharmaceuticals, Ltd.
- Applicants: NAL Pharmaceuticals Ltd.
- Inventors: Je Phil Ryoo; Chun Kwong Chu; Zheng Wang
- Web page: https://patentgrep.com/patent/US8771736B2

## CPC

- A61K 9/7015: {Drug-containing film-forming compositions, e.g. spray-on}
- 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}
- A61K 9/006: {Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays}
- 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)}
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- A61K 9/2027: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/7007: {Drug-containing films, membranes or sheets (A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence)}
- A61K 31/00: Medicinal preparations containing organic active ingredients
- A61K 31/192: having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid {(cannabinoids A61K31/658)}
- A61K 31/196: the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
- A61K 31/4045: Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
- A61K 31/4196: 1,2,4-Triazoles
- A61K 31/421: 1,3-Oxazoles, e.g. pemoline, trimethadione
- A61K 31/422: not condensed and containing further heterocyclic rings
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- A61K 31/4468: having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
- A61K 31/465: Nicotine; Derivatives thereof
- A61K 31/495: having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53})
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K 31/78: of acrylic acid or derivatives thereof
- A61K 38/05: Dipeptides
- A61K 38/06: Tripeptides
- 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
- A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K 47/38: Cellulose; Derivatives thereof
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A61P 1/08: for nausea, cinetosis or vertigo; Antiemetics
- A61P 1/10: Laxatives
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 15/10: for impotence
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/06: Antimigraine agents
- A61P 25/20: Hypnotics; Sedatives
- 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
- A61P 25/30: for treating abuse or dependence
- A61P 25/34: Tobacco-abuse
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Oral dosage forms and methods for delivering effective amounts of erectile dysfunction medicaments to patients to provide rapid uptake of said agents through the mucosa of the oral cavity are disclosed.

## Claims

### Claim 1

A fast onset pharmaceutical composition comprising:
a water soluble matrix comprising an effective amount of a pharmaceutically active agent selected from the group consisting of sildenafil, tadalafil, vardenafil and their pharmacologically acceptable salts and an absorption enhancer having an HLB of about 8 to about 16,
wherein the matrix is a film and the absorption enhancer is one or more sucrose fatty acid esters.

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 2)

The pharmaceutical composition of claim 2, wherein the nonionic surfactant is at least one or more of polysorbate and sorbitan fatty acid ester.

### Claim 4 (depends on 2)

The pharmaceutical composition of claim 2, further comprising a secondary absorption enhancer selected from the group consisting of glycerol, ginger oil, cineole and terpenes.

### Claim 5 (depends on 3)

The pharmaceutical composition of claim 3, 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.

### Claim 6 (depends on 3)

The pharmaceutical composition of claim 3, wherein the sorbitan fatty acid ester is selected from the group consisting of sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan tristearate and sorbitan monooleate.

### Claim 7 (depends on 1)

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.

### Claim 8 (depends on 1)

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

### Claim 9 (depends on 7)

The pharmaceutical composition of claim 7, wherein the film forming agent is pullulan.

### Claim 10 (depends on 7)

The pharmaceutical composition of claim 7, wherein the ratio of polyvinyl pyrrolidone to polymeric alginate in the polymeric mixture is from about 5:1 to about 1:3.

### Claim 11 (depends on 1)

The pharmaceutical composition of claim 1, wherein the sucrose fatty acid esters are sucrose fatty acid esters having a monomer content of from about 20 percent to about 80 percent.

### Claim 12 (depends on 1)

The pharmaceutical composition of claim 1, 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.

### Claim 13 (depends on 7)

The pharmaceutical composition of claim 7, 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.

### Claim 14 (depends on 1)

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

### Claim 15 (depends on 1)

The pharmaceutical composition of claim 1, wherein the film when placed in the oral cavity will dissolve in about 0.25 minutes to about 15 minutes.

### Claim 16 (depends on 1)

The pharmaceutical composition of claim 1, 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.

### Claim 17 (depends on 1)

The pharmaceutical composition of claim 1, 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.

### Claim 18 (depends on 7)

The pharmaceutical composition of claim 7, 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.

### Claim 19 (depends on 1)

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

### Claim 20 (depends on 1)

The pharmaceutical composition of claim 1, wherein said sucrose fatty acid ester is a C12 to C20 saturated fatty acid ester of sucrose.

### Claim 21 (depends on 1)

The pharmaceutical composition of claim 1, wherein said sucrose fatty acid ester is a sucrose stearate.

### Claim 22 (depends on 1)

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

### Claim 23 (depends on 1)

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

### Claim 24 (depends on 1)

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

### Claim 25

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.

### Claim 26 (depends on 25)

The method of claim 25, further comprising a polymeric mixture of polyvinyl pyrrolidone and a polymeric alginate.

### Claim 27 (depends on 26)

The method of claim 26, wherein the ratio of polyvinyl pyrrolidone to polymeric alginate in the polymeric mixture is from about 5:1 to about 1:3.

### Claim 28 (depends on 26)

The method of claim 26, 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.

### Claim 29 (depends on 25)

The method of claim 25, wherein said matrix is placed under the tongue of said patient.

### Claim 30 (depends on 25)

The method of claim 25, wherein said matrix is inserted on the buccal tissue of the mouth of the patient.

### Claim 31 (depends on 25)

The method of claim 25, wherein the sucrose fatty acid ester has a monomer content of from about 20 percent to about 80 percent.

### Claim 32 (depends on 25)

The method of claim 25, 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.

### Claim 33 (depends on 25)

The method of claim 25, wherein said fatty acid esters are present in an amount of from about 1% to about 20% based upon the weight of the film.

### Claim 34 (depends on 25)

The method of claim 25, 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.

### Claim 35 (depends on 25)

The method of claim 25, further comprising a secondary absorption enhancer selected from the group consisting of glycerol, tween, span, ginger oil, cineole and terpenes.

### Claim 36 (depends on 25)

The method of claim 25, wherein the matrix is a film.

### Claim 37 (depends on 25)

The method of claim 25, further comprising pullulan as a film forming agent.

### Claim 38 (depends on 25)

The method of claim 25, wherein the active agent is released over a period of time from about 0.25 minutes to about 15 minutes.