# US 11,992,558 B2 · Controlled release formulation comprising flavoxate

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- Number: US 11,992,558 B2
- Document ID: US11992558B2
- Status: Granted
- Kind: B2
- Application number: 17/261,858
- Filed: 2019-07-21
- Published: 2021-09-30
- Granted: 2024-05-28
- Earliest claimed: 2018-07-21
- Assignees: Sushma Paul Berlia
- Applicants: Sushma Paul Berlia
- Inventors: Sushma Paul Berlia; Nishant Berlia; Anupama Diwan; Sunder Singh Bhandari
- Web page: https://patentgrep.com/patent/US11992558B2

## CPC

- A61K 9/2077: {Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets}
- A61J 3/10: into the form of compressed tablets (tablet presses B30B11/00)
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/2009: {Inorganic compounds}
- A61K 9/2013: {Organic compounds, e.g. phospholipids, fats}
- 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 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2095: {Tabletting processes}
- A61K 9/2853: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)}
- A61K 9/2893: {Tablet coating processes (mechanical aspects A61J3/06)}
- A61K 31/4453: only substituted in position 1, e.g. propipocaine, diperodon
- A61K 31/453: containing a six-membered ring with oxygen as a ring hetero atom
- A61P 13/10: of the bladder
- 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)
- A61J: CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to a controlled release oral formulation comprising about 400 mg to about 800 mg of flavoxate salt as an active ingredient, suitable polymers, binders, and excipients, and lacking an acidifying agent. The present invention also provides a method of preparing the controlled release oral formulation of about 400 mg to 800 mg of flavoxate salt. The controlled release formulation of present invention may comprise micronized particles of drug. The controlled release formulation has a controlled release profile of up to 24 hours, that is pH independent, and that is alcohol dose dumping risk-free.

## Claims

### Claim 1

A controlled release oral formulation comprising about 400 to about 800 mg of flavoxate salt as an active ingredient and further comprising polyvinylpyrrolidone K30 (PVP K30) and/or colloidal silicon dioxide; wherein the formulation does not comprise an acidifying agent.

### Claim 2 (depends on 1)

The controlled release oral formulation of claim 1, wherein the flavoxate salt is flavoxate hydrochloride.

### Claim 3 (depends on 1)

The controlled release oral formulation of claim 1, further comprising one or more polymers selected from the group consisting of a methylcellulose, a polyvinyl alcohol, an acrylic copolymer, an ethylcellulose, and a hydroxypropylmethyl-cellulose (HPMC).

### Claim 4 (depends on 1)

The controlled release oral formulation of claim 1, wherein the formulation further comprises one or more polymers, wherein the formulation comprises a ratio of polymers to flavoxate salt of about 1:8 to about 1:100.

### Claim 5 (depends on 1)

The controlled release oral formulation of claim 1, wherein the formulation further comprises one or more binders, wherein the formulation comprises a ratio of binders to flavoxate salt of about 1:16.

### Claim 6 (depends on 5)

The controlled release oral formulation of claim 5, wherein the one or more binders is dispersed in water, ethanol, acetonitrile, acetone, isopropyl alcohol, or a mixture thereof.

### Claim 7 (depends on 1)

The controlled release oral formulation of claim 1, further comprising one or more excipients selected from the group consisting of magnesium stearate, talc, colloidal silicon dioxide, isopropyl alcohol, and lactose.

### Claim 8 (depends on 1)

The controlled release oral formulation of claim 1, wherein the formulation is in a solid dosage form.

### Claim 9 (depends on 8)

The controlled release oral formulation of claim 8, wherein the solid dosage form is a tablet having a thickness of about 6.20 mm to about 6.90 mm.

### Claim 10 (depends on 8)

The controlled release oral formulation of claim 8, wherein the tablet has a hardness of about 6 kg/cm2 to about 20 kg/cm2.

### Claim 11 (depends on 9)

The controlled release oral formulation of claim 9, wherein the tablet comprises micronized granules of the flavoxate salt of particle size with D90 of about 10 μm to about 100 μm.

### Claim 12 (depends on 1)

The controlled release oral formulation of claim 1, wherein the formulation exhibits a pH-independent release profile of the flavoxate salt.

### Claim 13 (depends on 2)

The controlled release oral formulation of claim 2, wherein the formulation releases flavoxate hydrochloride throughout a course of 12-24 hours.

### Claim 14 (depends on 1)

The controlled release oral formulation of claim 1, wherein the formulation releases flavoxate salt over 24 hours, achieving a plasma concentration of flavoxate salt of 1 mcg/ml for 24 hours in a patient, wherein at least 10-15% of the flavoxate salt is released within the first hour, achieving a plasma concentration of flavoxate salt greater than or equal to 1 mcg/ml in the patient.

### Claim 15 (depends on 14)

The controlled release oral formulation of claim 14, wherein the formulation achieves a plasma concentration of 3-methylflavone-8-carboxylic acid (MFCA) greater than or equal to 1 mcg/ml in the first to two and a half hours.

### Claim 16

A formulation comprising about 400 mg to about 800 mg flavoxate salt as an active ingredient, HPMC K4M, and HPMC K15M, wherein the formulation further comprises PVP K30 and/or colloidal silicon dioxide and does not comprise an acidifying agent.

### Claim 17 (depends on 16)

The formulation of claim 16, wherein the formulation comprises about 82% (w/w %) flavoxate salt.

### Claim 18 (depends on 16)

The formulation of claim 16, wherein the flavoxate salt is flavoxate hydrochloride.

### Claim 19 (depends on 16)

The formulation of claim 16, wherein the formulation comprises colloidal silicon dioxide.

### Claim 20 (depends on 16)

The formulation of claim 16, wherein the formulation comprises about 0.5% to about 5% HPMC K4M, about 8% to about 15% HPMC K15M, about 0.5% to about 2% HPMC K100M, about 4% to about 6% PVP K30M, about 0.8% to about 1% magnesium stearate, up to about 1% colloidal silicon dioxide, and up to about 5% lactose, and optionally further comprises about 1% to about 3% talc.

### Claim 21 (depends on 16)

The formulation of claim 16, wherein the formulation comprises about 0.5% to about 5% HPMC K4M, about 4% to about 15% HPMC K15M, about 0.5% to about 2% HPMC K100M, about 4% to about 6% PVP K30, about 0.5% to about 5% lactose, about 0.8% to about 1% magnesium stearate, and up to about 1 colloidal silicon dioxide, and optionally further comprises about 1% to about 3% talc.

### Claim 22 (depends on 16)

The formulation of claim 16, comprising about 400 mg, about 600 mg, or about 800 mg flavoxate hydrochloride.

### Claim 23 (depends on 16)

The formulation of claim 16, comprising about 800 mg flavoxate hydrochloride, about 19.5 mg HPMC K4M, about 58.5 mg HPMC K15M, about 8 mg HPMC K100M, about 48.5 mg PVP K30, about 10 mg magnesium stearate, about 25 mg lactose, and about 4 mg colloidal silicon dioxide.

### Claim 24 (depends on 16)

The formulation of claim 16, comprising about 800 mg flavoxate hydrochloride, about 100 mg HPMC K15M, about 8 mg HPMC K100M, about 50 mg PVP K30, about 10 mg magnesium stearate, and about 4 mg colloidal silicon dioxide.

### Claim 25 (depends on 16)

The formulation of claim 16, wherein the formulation releases flavoxate salt with a 12 hour to 24 hour release profile.

### Claim 26 (depends on 16)

The formulation of claim 16, wherein the formulation exhibits a release profile of (a) 5-30% in 1 hour; (b) 45-85% in 8 hours, and (c) not less than 85% in 24 hrs.

### Claim 27 (depends on 16)

The formulation of claim 16, wherein the formulation exhibits a pH-independent release profile.

### Claim 28 (depends on 16)

The formulation of claim 16, wherein the formulation releases flavoxate salt over 24 hours, achieving a plasma concentration of flavoxate salt of 1 mcg/ml for 24 hours in a patient, wherein at least 10-15% of the flavoxate salt is released within the first hour, achieving a plasma concentration of flavoxate salt greater than or equal to 1 mcg/ml in the patient.

### Claim 29 (depends on 1)

A method of treating at least one symptom of nocturia, dysuria, urgency, vesicle suprapubic pain, frequency, or urinary incontinence, associated with cystitis, prostatitis, urethritis, urethrocystitis, urethrotrigonitis, or symptoms of overactive bladder, wherein the method comprises administering the formulation of claim 1 to a patient in need thereof.

### Claim 30 (depends on 3)

The controlled release oral formulation of claim 3, wherein the HPMC is chosen from the group consisting of HPMC K4M, HPMC K15M, and HPMC K100M.