Process for preparing tannate liquid and semi-solid dosage forms

• US 6,869,618 B2
• Filed: 04/09/2002
• Issued: 03/22/2005
• Est. Priority Date: 04/10/2001
• Status: Expired due to Fees

• Current Assignee: Pernix Therapeutics, LLC (Currax Holdings USA, LLC)
• Original Assignee: Kiel Laboratories
• Inventors: Kiel, Jeffrey S., Thomas, H. Greg, Mani, Narasimhan
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Sheikh, Humera N.
• Application Number:
  US10/119,285
• Publication Number:
  US 20030050252A1
• Time in Patent Office: 1,078 Days
• Field of Search: 424/489, 514/849, 514/850, 514/853, 514/855, 514/937, 514/653, 514/352
• US Class Current: 424/489
• CPC Class Codes: A61K 31/205 Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
• CPC Class Codes: A61K 31/7024 Esters of saccharides
• CPC Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy
• CPC Class Codes: A61K 9/2004 Excipients; Inactive ingredients
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds

Abstract

An active ingredient from the group of an antihistamine, a decongestant, an antitussive or anticholinergic is dissolved in a suitable solvent and added to a dispersion of tannic acid in water to form the tannate salt complex of the active ingredient. The active ingredient tannate salt complex without isolation or purification is then added to a liquid or semi-solid medium composed of thickening, suspending, coloring, sweetening and flavoring agents, with stirring. Thereafter, preservatives, pH-adjusting and anti-caking agents in a suitable solvent are mixed with the liquid or semi-solid medium to generate a therapeutic dosage form.

Claims

1. A manufacturing process for the in-situ conversion and incorporation of a salt or free base of an active pharmaceutical ingredient selected from the group consisting of an antihistamine, a decongestant, an antitussive and an anticholinergic for incorporation into a therapeutic liquid or semi-solid dosage form, the process comprising the steps of:

(a) dissolving the salt or free base of the active pharmaceutical ingredient in a pharmaceutically acceptable liquid to form a solution;

at

(b) separately adding a dispersing agent comprising magnesium aluminum silicate, xanthan gum or mixtures thereof and tannic acid to a pharmaceutically acceptable liquid to form a dispersion;

(c) transferring the solution from step (a), to the dispersion in step (b) to form a precipitate of a tannate salt complex of the active pharmaceutical ingredient; and

(d) combining the tannate salt complex of the active pharmaceutical ingredient without isolation or purification with a pharmaceutically acceptable excipient to generate a therapeutic dosage form.

2. The process according to claim 1 wherein the antihistamine active pharmaceutical ingredient is selected from the group consisting of:

Carbinoxamine,

Chlorpheniramine,

Pyrilamine,

Pheniramine,

Phenindamine,

Diphenhydramine,

Bromodiphenhydramine

Brompheniramine,

Loratadine,

Desloratadine,

Fexofenadine,

Cetirizine,

Hydroxyzine,

Promethazine,

Acrivastin,

Triprolidine,

Meclizine,

Dimenhydrinate,

Triplermamine

Doxylamine,

Diphenylpyrilamine,

Trimeprazine; and

Cholorcylizine.

3. The process according to claim 1 wherein the antitussive active pharmaceutical ingredient is selected from the group consisting of.

Carbetapentane,

Dextromethorphan,

Diphenhydramine,

Codeine,

Hydrocodone,

Oxycodone;

and

Morphine.

4. The process according to claim 1 wherein the decongestant active pharmaccutical ingredient is selected from the group consisting of:

Phenylephrine,

Pseudoephedrine,

Ephedrine,

Diphenhydramine,

Cyproheptadine,

Phenyltoloxamine, and

Clemastine.

5. The process according to claim 1 wherein the antihistamine and decongestant active ingredients are provided as the bitartrate, maleate, citrate, chloride, bromide, acetate or sulfate salt.

6. The process according to claim 1 wherein the tannic acid provided in step (b) is natural or synthetic.

7. The process according to claim 1 wherein the pharmaceutically acceptable liquid in steps (a) and (b) is selected from the group consisting of purified water, isopropyl alcohol, ethanol, glycerin, propylene glycol, mineral oil and mixtures thereof.

8. The process according to claim 7 wherein the pharmaceutically acceptable liquid in steps (a) and (b) is purified water.

9. The process according to claim 1 wherein the pharmaceutically acceptable excipient is selected from a group consisting of sucrose, saccharin sodium, an artificial flavor, kaolin, pectin, xanthan gum, magnesium aluminum silicate, glycerin, sodium citrate, sodium phosphate monobasic, sodium phosphate dibasic, citric acid, sodium benzoate, benzoic acid, methylparaben, a coloring agent and mixtures thereof.