# US 5,705,190 A · Controlled release formulation for poorly soluble basic drugs

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- Number: US 5,705,190 A
- Document ID: US5705190A
- Status: Granted
- Kind: A
- Application number: 08/574,877
- Filed: 1995-12-19
- Granted: 1998-01-06
- Earliest claimed: 1995-12-19
- Assignees: Abbott Laboratories
- Inventors: Neville W. Broad; Alan F. Carmody; Liam C. Feely; Brian C. Withers
- Web page: https://patentgrep.com/patent/US5705190A

## CPC

- A61K 31/7052: having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K 9/2013: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/205: {Polysaccharides, e.g. alginate, gums; Cyclodextrin}
- A61K 31/165: having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K 31/4045: Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
- A61K 31/4164: 1,3-Diazoles
- A61K 31/5513: 1,4-Benzodiazepines, e.g. diazepam {or clozapine}
- A61K 31/7048: having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin}
- A61K 31/706: containing six-membered rings with nitrogen as a ring hetero atom
- A61P 31/02: Local antiseptics
- 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 controlled release, oral, solid, pharmaceutical composition for a reduced daily dosage regimen is described where the therapeutic ingredient is a poorly soluble basic drug. The formulation comprises the use of a water-soluble alginate salt, a complex salt of alginic acid and an organic carboxylic acid in admixture with the therapeutic drug. A particular embodiment comprising a once a day dosage form for clarithromycin is also described.

## Claims

### Claim 1

A controlled release, solid pharmaceutical composition adapted for oral administration comprising:
a therapeutically effective amount of at least one basic drug having a water solubility of less than 1 part per 30 parts water;
a water-soluble alginate salt;
a complex salt of alginic acid, wherein the cation yielding an insoluble salt is selected from the group consisting of calcium, strontium, iron, and barium;
and an organic carboxylic acid to facilitate dissolution of the basic drug, wherein the weight ratio of the water-soluble salt to the complex salt of alginic acid varies from 16:1 to 1:1, and the molar ratio of the carboxylic acid to the drug varies from 0.2:1 to 5:1.

### Claim 2 (depends on 1)

The composition of claim 1, in tablet form.

### Claim 3 (depends on 1)

The composition of claim 1, in the form of a once a day dosage regimen.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the basic drug is a macrolide.

### Claim 5 (depends on 4)

The composition of claim 4, wherein the macrolide is clarithromycin.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the water-soluble alginate salt is sodium alginate.

### Claim 7 (depends on 1)

The composition of claim 1, wherein the complex salt of alginic acid is sodium-calcium alginate.

### Claim 8 (depends on 1)

The composition of claim 1, wherein the organic carboxylic acid is selected from the group consisting of tartaric, malic, succinic, glutaric, glutamic, maleic, mandelic and citric acid.

### Claim 9 (depends on 8)

The composition of claim 8, wherein the organic carboxylic acid is citric acid.

### Claim 10 (depends on 1)

The composition of claim 1, wherein the weight ratio of sodium alginate to sodium-calcium alginate is about 16:1 to 1:1.

### Claim 11 (depends on 1)

The composition of claim 1, wherein the weight ratio of sodium alginate to sodium-calcium alginate is about 8:1 to 2:1.

### Claim 12 (depends on 1)

The composition of claim 1, wherein the molar ratio of organic acid to basic drug is about 1:1.

### Claim 13 (depends on 1)

The composition of claim 1, wherein the basic drug is selected from the group consisting of sulfamethoxazole, metronidazole, cimetidine, indapamide, atenolol and diazepam.

### Claim 14 (depends on 4)

The composition of claim 4, wherein the macrolide is selected from the group consisting of erythromycin, dirithromycin, azithromycin, roxithromycin and ABT-229.

### Claim 15

A controlled release, solid pharmaceutical composition adapted for oral administration of a once a day dosage regimen comprising:
about 500 mg of clarithromycin;
from about 75 to 400 mg of sodium alginate; from about 10 to 400 mg of sodium-calcium alginate, and about 128 mg of citric acid.

### Claim 16 (depends on 14)

The composition of claim 14 comprising:
from about 80 to 200 mg of sodium alginate, and
from about 10 to 40 mg of sodium-calcium alginate.

### Claim 17 (depends on 15)

The composition of claim 15 comprising:
about 120 mg of sodium alginate, and
about 15 mg of sodium-calcium alginate.