# US 10,869,877 B2 · Controlled release doxycycline

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,869,877 B2
- Document ID: US10869877B2
- Status: Granted
- Kind: B2
- Application number: 16/297,410
- Filed: 2019-03-08
- Published: 2019-07-04
- Granted: 2020-12-22
- Earliest claimed: 2014-10-08
- Assignees: Mayne Pharma International Pty Ltd.
- Applicants: Mayne Pharma International Pty Ltd.
- Inventors: Stefan Lukas; Angelo Lepore; Stuart Mudge
- Web page: https://patentgrep.com/patent/US10869877B2

## CPC

- A61K 31/65: Tetracyclines
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2081: {with microcapsules or coated microparticles according to A61K9/50}
- A61K 9/5042: {Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose}
- A61K 9/5047: {Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose}
- 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)

## Abstract

The disclosure provides controlled release compositions comprising tetracyclines and in some embodiments, doxycycline. The controlled release doxycycline compositions of the invention exhibit a superior dissolution profile and provide reduced side effects such as nausea and irritation.

## Claims

### Claim 1

A dosage form, comprising a plurality of modified release doxycycline salt pellets, wherein the doxycycline salt pellets comprise a doxycycline salt core and a controlled release polymer composition disposed over the core,
wherein said controlled release polymer composition comprises a blend of hydroxypropyl methylcellulose phthalate and hydroxypropyl methyl cellulose;
wherein said dosage form comprises doxycycline salt in an amount equivalent to 60, 90, or 120 mg of doxycycline base;
wherein said dosage form comprising doxycycline salt maintains doxycycline base release levels measured under USP <711> conditions at pH 5 that provide a clinically effective plasma level of doxycycline base;
wherein said dosage form releases less than 15% of the doxycycline at pH 1.2 and less than 40% of the doxycycline at pH 4.5 after 60 minutes; and
wherein after administration of a single dose under fasting conditions to a patient in need thereof, the average AUC0-∞ is 80% to 125% of 200-300 ng·hr/ml per mg of doxycycline base administered.

### Claim 2 (depends on 1)

The dosage form of claim 1, wherein the average AUC0-∞ is 80% to 125% of 220-225 ng·hr/ml per mg of doxycycline base administered.

### Claim 3 (depends on 1)

The dosage form of claim 1, wherein said dosage form comprises doxycycline salt in an amount equivalent to 60 mg of doxycycline base and after administration of a single dose under fasting conditions to a patient in need thereof, the average AUC0-∞ is 13345±1000 ng·hr/ml.

### Claim 4 (depends on 1)

The dosage form of claim 1, wherein said dosage form comprises doxycycline salt in an amount equivalent to 120 mg of doxycycline base and after administration of a single dose under fasting conditions to a patient in need thereof, the average AUC0-∞ is 26690±1000 ng·hr/ml.

### Claim 5 (depends on 1)

The dosage form of claim 1, wherein after administration of a single dose under fasting conditions to a patient in need thereof, the average Cmax is 80% to 125% of 10-20 ng/ml per mg of doxycycline base administered.

### Claim 6 (depends on 5)

The dosage form of claim 5, wherein the average Cmax is 80% to 125% of 10-15 ng/ml per mg of doxycycline base administered.

### Claim 7 (depends on 1)

The dosage form of claim 1, wherein said dosage form comprises doxycycline salt in an amount equivalent to 60 mg of doxycycline base and after administration of a single dose under fasting conditions to a patient in need thereof, the average Cmax is 809±100 ng/ml.

### Claim 8 (depends on 1)

The dosage form of claim 1, wherein said dosage form comprises doxycycline salt in an amount equivalent to 120 mg of doxycycline base and after administration of a single dose under fasting conditions to a patient in need thereof, the average Cmax is 1619±100 ng/ml.

### Claim 9 (depends on 1)

The dosage form of claim 1, wherein at pH 5 the normalized average release of doxycycline base measured under USP <711> conditions is at least one of:
less than 48% at 15 minutes;
less than 64% at 20 minutes; and
less than 72% at 25 minutes.

### Claim 10 (depends on 1)

The dosage form of claim 1, wherein at pH 5 the normalized average release of doxycycline base measured under USP <711> conditions is at least one of:
30% to 48% at 15 minutes;
30% to 64% at 20 minutes; and
45% to 72% at 25 minutes.

### Claim 11 (depends on 1)

The dosage form of claim 1, wherein at pH 5 the normalized average release of doxycycline base measured under USP <711> conditions is at least one of:
35% to 48% at 15 minutes;
40% to 64% at 20 minutes; and
50% to 72% at 25 minutes.

### Claim 12 (depends on 1)

The dosage form of claim 1, wherein at pH 5 the normalized average release of doxycycline base measured under USP <711> conditions at 20 minutes ranges from 42% to 64%.

### Claim 13 (depends on 1)

The dosage form of claim 1, wherein at pH 5 the normalized average release of doxycycline base measured under USP <711> conditions at 20 minutes ranges from 47% to 64%.

### Claim 14 (depends on 1)

The dosage form of claim 1, wherein at pH 5 the normalized average release of doxycycline base measured under USP <711> conditions at 25 minutes ranges from 58% to 72%.

### Claim 15 (depends on 1)

The dosage form of claim 1, wherein at pH 5 the normalized average release of doxycycline base measured under USP <711> conditions at 25 minutes ranges from 65% to 72%.

### Claim 16 (depends on 1)

The dosage form of claim 1, wherein said doxycycline salt pellets are contained in a capsule or tablet.

### Claim 17 (depends on 1)

The dosage form of claim 1, wherein the doxycycline salt is doxycycline hyclate.

### Claim 18 (depends on 1)

The dosage form of claim 1, wherein the release of doxycycline base is measured under USP <711> conditions comprising: rotating the dosage form in a USP Apparatus 1 basket at 100 RPM, within 900 mL of a dissolution media comprising acid or buffer, which is held at a temperature of 37° C.

### Claim 19 (depends on 18)

The dosage form of claim 18, wherein said dosage form is a tablet.

### Claim 20 (depends on 1)

The dosage form of claim 1, wherein the release of doxycycline base is measured under USP <711> conditions comprising: rotating the dosage form in a USP Apparatus 1 basket at 50 RPM, within 900 mL of a dissolution media comprising acid or buffer, which is held at a temperature of 37° C.

### Claim 21 (depends on 1)

The dosage form of claim 1, wherein the controlled release polymer composition further comprises a plasticizer.

### Claim 22 (depends on 21)

The dosage form of claim 21, wherein the plasticizer is selected from the group consisting of citric acid esters, tartaric acid esters, glycerol, glycerol esters, phthalic acid esters, adipic acid esters, sebacic acid esters, polyethylene glycol esters, sorbitan esters, and combinations thereof.

### Claim 23 (depends on 22)

The dosage form of claim 22, wherein the controlled release polymer composition consists essentially of hydroxypropyl methylcellulose phthalate, hydroxypropyl methyl cellulose, and triethylcitrate.

### Claim 24 (depends on 1)

The dosage form of claim 1, wherein the ratio of hydroxypropyl methylcellulose phthalate to hydroxypropyl methylcellulose ranges from about 3.5:1 to about 6:1.

### Claim 25 (depends on 1)

The dosage form of claim 1, wherein the ratio of hydroxypropyl methylcellulose phthalate to hydroxypropyl methylcellulose ranges from about 3.5:1 to about 6:1.