# US 2019/0314293 A1 · Loxapine film oral dosage form

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- Number: US 2019/0314293 A1
- Document ID: US20190314293A1
- Status: Published application
- Kind: A1
- Application number: 16/455,916
- Filed: 2019-06-28
- Published: 2019-10-17
- Earliest claimed: 2016-02-03
- Assignees: Intelgenx Corp.
- Applicants: Intelgenx Corp.
- Inventors: Mobarik Bilal; Rodolphe Obeid; Nadine Paiement
- Web page: https://patentgrep.com/patent/US20190314293A1

## CPC

- A61K 9/7007: {Drug-containing films, membranes or sheets (A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence)}
- A61K 9/006: {Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays}
- A61K 31/553: having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- 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
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/22: Anxiolytics
- 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

A loxapine film oral dosage form includes loxapine salt, free base, or prodrug in an amount effective to provide relief from acute agitation associated with schizophrenia or bipolar 1 disorder via oral transmucosal delivery, dispersed in a polymeric film forming system. Advantageously, the film oral dosage form further includes a sweetener, a refreshing agent, an antioxidant, a pH stabilizer, a penetration enhancer, a mucoadhesive agent and a plasticizer. The loxapine film oral dosage form provides rapid onset of relief from acute agitation associated with schizophrenia or bipolar 1 disorder without presenting pulmonary health risks, thereby reducing risks to patients and others.

## Claims

### Claim 1

A loxapine film oral dosage form, comprising:
loxapine salt, free base, or prodrug in an amount that is effective to provide relief from acute agitation associated with schizophrenia or bipolar 1 disorder via transmucosal delivery route;
a pH stabilizer added in an amount of from 0.5% to 10% of the weight of the film oral dosage form, which amount of pH stabilizer is sufficient to maintain a neutral pH of from 6 to 8 to enhance absorption of the loxapine salt, free base or prodrug through oral mucosa;
a penetration enhancer in an amount effective to promote absorption of loxapine via oral mucosa; and
the loxapine salt, free base, or prodrug dispersed in a polymeric film forming system including at least one film forming polymer, the film forming system formulated to reside in the buccal cavity or sublingual region of a subject being administered the loxapine film oral dosage form for a period of from 10 minutes to one hour, wherein the film forming system includes polyvinylpyrrolidone in an amount of 5% to 50% of the weight of the film oral dosage form, which amount of polyvinylpyrrolidone is sufficient to concurrently maintain neutral pH of from 6 to 8 during absorption of the loxapine salt, free base or prodrug through oral mucosa while maintaining the loxapine salt, free base or prodrug in a highly dissolved form to promote rapid transmucosal absorption and rapid onset of a therapeutic effect.

### Claim 2 (depends on 1)

The loxapine film oral dosage form of claim 1, wherein the penetration enhancer comprises sodium hyaluronate.

### Claim 3 (depends on 1)

The loxapine film oral dosage form of claim 1, wherein the penetration enhancer comprises sodium taurodeoxycholate.

### Claim 4 (depends on 1)

The loxapine film oral dosage form of claim 1, wherein the penetration enhancer comprises sodium glycodeoxycholate.

### Claim 5 (depends on 1)

The loxapine film oral dosage form of claim 1, further comprising a sweetener.

### Claim 6 (depends on 1)

The loxapine film oral dosage form of claim 1, further comprising a refreshing agent.

### Claim 7 (depends on 1)

The loxapine film oral dosage form of claim 1, further comprising an antioxidant.

### Claim 8 (depends on 1)

The loxapine film oral dosage form of claim 1, further comprising a mucoadhesive agent.

### Claim 9 (depends on 1)

The loxapine film oral dosage form of claim 1, further comprising a plasticizer.

### Claim 10 (depends on 1)

The loxapine film oral dosage form of claim 1, further comprising sulfite salts in an amount effective to promote the stability of the film.

### Claim 11 (depends on 1)

The loxapine film oral dosage form of claim 1, further comprising polyethylene glycol in an amount effective to increase the flexibility of the film.

### Claim 12 (depends on 1)

A process of preparing a loxapine film oral dosage form of claim 1, comprising:
dissolving or suspending the loxapine salt, free base or prodrug, pH stabilizer, penetration enhancer, and a polymeric film forming system in a solvent to produce a film formulation;
dispersing the film formulation on a substrate;
removing the solvent from the film formulation to produce a dry film; and
cutting the film into individual dosage forms.

### Claim 13 (depends on 12)

The process of claim 12, in which the solvent comprises methanol and/or ethanol.

### Claim 14 (depends on 12)

The process of claim 12, in which the solvent comprises a combination of methanol and/or ethanol and water.

### Claim 15 (depends on 12)

The process of claim 12, further comprising adding polyethylene glycol to the film formulation in an amount effective to increase the flexibility of the film.

### Claim 16 (depends on 12)

The loaxapine film oral dosage form of claim 12, further comprising sulfite salts in an amount effective to promote the stability of the film.

### Claim 17 (depends on 12)

The process of claim 12, wherein the penetration enhancer comprises sodium hyaluronate.

### Claim 18 (depends on 12)

The process of claim 12, wherein the penetration enhancer comprises sodium taurodeoxycholate.

### Claim 19 (depends on 12)

The process of claim 12, wherein the penetration enhancer comprises sodium glycodeoxycholate.