# US 10,869,839 B2 · Extended release compositions comprising trihexyphenidyl

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- Number: US 10,869,839 B2
- Document ID: US10869839B2
- Status: Granted
- Kind: B2
- Application number: 16/864,638
- Filed: 2020-05-01
- Published: 2020-08-20
- Granted: 2020-12-22
- Earliest claimed: 2018-09-21
- Assignees: Kashiv Biosciences, LLC
- Applicants: Kashiv Biosciences, LLC
- Inventors: Namdev B. Shelke; Siva Ram Kiran- Vaka; Navnit H. Shah; Dipen Desai; Wantanee Phuapradit
- Web page: https://patentgrep.com/patent/US10869839B2

## CPC

- A61K 9/2886: {having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer (of the type active core-drug layer-inactive layer A61K9/209)}
- A61K 9/5042: {Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/501: {Inorganic compounds}
- A61K 9/5047: {Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose}
- A61K 9/5078: {with drug-free core}
- A61K 9/5089: {Processes}
- A61K 31/4453: only substituted in position 1, e.g. propipocaine, diperodon
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- 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

The present disclosure provides extended release trihexyphenidyl compositions suitable for once- or twice-daily administration. The compositions comprise a core comprising organic acid that is coated with at least one drug layer comprising trihexyphenidyl hydrochloride, and a functional coat over the drug-layered core. The extended release compositions of the disclosure provide reduced Cmax, a Cmin:Cmax ratio of ≥0.4, and extended release, while maintaining therapeutically effective concentration, of trihexyphenidyl for at least about 16 hours. The compositions of the disclosure improve solubility of trihexyphenidyl hydrochloride, at a pH of greater than or equal to 5, to maintain its minimum effective concentration at such pH.

## Claims

### Claim 1

A pharmaceutical pellet composition comprising:
a) a core comprising an organic acid;
b) a first drug layer covering at least a portion of the core; and
c) a functional coat covering at least a portion of the first drug layer,
wherein the first drug layer comprises trihexyphenidyl hydrochloride and a nonionic water-soluble polymer,
wherein the functional coat comprises a nonionic water-insoluble polymer and a pore former, wherein the nonionic water-insoluble polymer and the pore former are present in a weight ratio of between about 80:20 and about 98:2,
wherein the functional coat has a coating weight gain of between about 10% w/w and about 40% w/w, based on the total weight of the pellet without the functional coat,
wherein the trihexyphenidyl hydrochloride and the organic acid are present in a weight ratio of between about 1:5 and about 1:15,
wherein the organic acid provides an acid microenvironment within the dosage form and improves the solubility of the trihexyphenidyl hydrochloride, in the portions of the GI tract with a pH of greater than or equal to 5, to maintain a minimum therapeutic plasma concentration of the trihexyphenidyl hydrochloride at such pH, and
wherein the composition provides extended release of the trihexyphenidyl hydrochloride, with a Cmin:Cmax ratio of >0.4, for a period of at least about 16 hours.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the trihexyphenidyl hydrochloride is present in an amount of from about 50% w/w to about 60% w/w, based on the total weight of the first drug layer.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the organic acid is selected from the group comprising tartaric acid, citric acid, fumaric acid, succinic acid, malic acid, and combinations thereof.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the nonionic water-soluble polymer in the drug layer is selected from the group comprising hydroxypropyl cellulose, methyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, polyethylene glycol, polyvinyl alcohol, poloxamer, and mixtures thereof.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the nonionic water-insoluble polymer in the functional coat is selected from the group consisting of ethyl cellulose, cellulose acetate, cellulose diacetate, cellulose triacetate, cellulose propionate, a polyvinyl acetate dispersion, and combinations thereof.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the pore former is an enteric polymer selected from the group consisting of cellulose acetate phthalate, cellulose acetate succinate, methylcellulose phthalate, hydroxyethyl cellulose phthalate, polyvinyl acetate phthalate, polyvinyl butyrate acetate, vinyl acetate-maleic anhydride copolymer, methacrylic acid copolymer, hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, cellulose acetyl phthalate, and mixtures thereof.

### Claim 7 (depends on 1)

The composition of claim 1, wherein the pore former is a nonionic, water-soluble polymer comprising methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, polyethylene glycol, polyvinyl alcohol, poloxamer, and mixtures thereof.

### Claim 8 (depends on 1)

The composition of claim 1, wherein the nonionic water-insoluble polymer is ethyl cellulose and the pore former is hydroxypropyl methylcellulose phthalate.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the composition further comprises a second drug layer comprising trihexyphenidyl hydrochloride.

### Claim 10 (depends on 1)

The composition of claim 1, wherein the composition maintains the concentration of trihexyphenidyl hydrochloride in plasma from about 1 ng/ml to about 20 ng/ml for a period of at least about 16 hours.

### Claim 11 (depends on 1)

The composition of claim 1, wherein the composition provides extended release of trihexyphenidyl hydrochloride for about 24 hours.