BG107987A - Liquid form of combined medicamentous preparation for the treatment of colds and flue diseases - Google Patents

Abstract

The invention relates to a liquid medicamentous form of a preparation for the treatment of colds and 'flue diseases, comprising acetaminophene (paracetamol), chlorpheniramine maleate, dextrometorphan, hydrobromide and pseudophedrine hydrochloride. The composition of the medicamentous form ensures the complete dissolution of the acatminophene and its chemical and physico-chemical stability in the proposed composition. The medicamentous form is a clear physico-chemically-stable solution with pH 5.0 0.5 and shelf life of 3 years.

Description

TECHNICAL FIELD

The invention relates to a liquid dosage form for the treatment of colds and influenza diseases comprising acetaminophen (paracetamol), chloropheniramine maleate, dextromethorphan hydrobromide and pseudoephedrine hydrochloride.

BACKGROUND OF THE INVENTION

A preparation comprising acetaminophen (paracetamol), chlorpheniramine maleate, dextromethorphan hydrobromide and pseudoephedrine hydrochloride, in liquid form, in which the excipients described are 10% alcohol, benzoic acid, glycerin, polyethylene glycol, polyethylene glycol, polyethylene glycol, coloring agent, flavoring agents and water [Phisicians'Desk Reference, Ed. 1994, p.678].

The combination of analgesic - paracetamol, antihistamine - chlorpheniramine maleate, decongenstant - pseudoephedrine hydrochloride and expectorant dextromethorphan hydrobromide make the drug effective for both cold and flu. It is used in conditions of general malaise, stuffy nose, sore throat, cough, headache and fever.

_d The presence of four active substances with different physicochemical properties creates problems in the formulation and stabilization of a liquid oral dosage form. Acetaminophen in aqueous solution is known to hydrolyze to p-aminophenol, which in turn decomposes to quinonym. The decay rate increases with increasing temperature and light. In addition, it is known that due to hydrolysis, paracetamol is unstable in acidic and alkaline environments (Pat. RU 2 192 249).

The problem to be solved with the invention is to provide a liquid oral dosage form of acetaminophen (paracetamol), chlorophenyramine maleate, dextromethorphan hydrobromide and pseudoephedrine hydrochloride, which is a clear solution with a pH of 4.5 to 5.5 with a stable pH of 5.5 to 5.5. 3 years.

SUMMARY OF THE INVENTION

The problem is solved by a liquid dosage form of a combination agent containing acetaminophen (paracetamol), chlorpheniramine maleate, dextromethorphan hydrobromide and pseudoephedrine hydrochloride containing a mixed solvent consisting of propylene glycol, 1% ethylene glycol, 1 ethylene glycol, 1 ethylene glycol 4: 0.5 to 2; pH 5.0 ± 0.5 buffer of sodium citrate and citric acid; disodium edetate from 0.01 to 0.05 w / v %; polyvinylpyrrolidone from 0.01 to 1.5 w / v %; sorbitol from 10.0 to 40.0 w / v %; saccharin sodium from 0.05 to 0.30 w / v %. The dosage form contains the usual preservatives, coloring agent, flavoring substance and water up to 100 ml.

The solvent used provides both the complete dissolution of acetaminophen and its chemical and physico-chemical stability in the proposed composition. The dosage form is a clear physico-chemically stable solution with a pH of 5.0 ± 0.5 and a shelf life of 3 years.

EXAMPLES

EXAMPLE I

Composition for 100 ml syrup, g:

Acetaminophen

3,300

Chlorophenyramine maleate

0.013

Dextromethorphan hydrobromide100

Pseudoephedrine hydrochloride0,200

Methyl parahydroxybenzoate 0,100

Propyl parahydroxybenzoate 0,020

Sodium citrate0.400

Citric acid0.300

Disodium edetate0.040

Sorbitol 30,000

Saccharin sodium0,200

Propylene glycol 10,000

Polyethylene glycol 400 15,000

Ethanol 96% 10,000 • · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

Polyvinylpyrrolidone 1,000 A flavoring substance q.s. Coloring q.s. Purified water up to 100 ml EXAMPLE II Composition for 100 ml syrup, g: Acetaminophen 3,300 Chlorophenyramine maleate 0.013 Dextromethorphan hydrobromide 0.100 Pseudoephedrine hydrochloride 0,200 Methyl parahydroxybenzoate 0.100 Propyl parahydroxybenzoate 0.020 Sodium citrate .400 Citric acid 0.300 Disodium edetate 0.025 Sorbitol 20,000 Saccharin sodium 0.050 Propylene glycol 5,000 Polyethylene glycol 400 20,000 Ethanol 96% 10,000 Polyvinylpyrrolidone 0.030 A flavoring substance q.s. Coloring q.s. Purified water up to 100 ml EXAMPLE III Composition for 100 ml syrup, g: Acetaminophen 3,300 Chlorophenyramine maleate 0.013 Dextromethorphan hydrobromide 0.100 Pseudoephedrine hydrochloride 0,200

• · · · · »· ·· 4 · 4« * ···· ·· 4 * 4 · • · · 44 · * 44 *

4 4 4 4 4 4

Methyl parahydroxybenzoate 0.100 Propyl parahydroxybenzoate 0.020 Sodium citrate .400 Citric acid 0.300 Disodium edetate 0.050 Sorbitol 35,000 Saccharin sodium 0.300 Propylene glycol 5,000 Polyethylene glycol 400 15,000 Ethanol 96% 5,000 Polyvinylpyrrolidone 1,500 A flavoring substance q.s. Coloring q.s. Purified water up to 100 ml

EXAMPLE IV

The stability of the liquid form was examined under the following storage conditions:

- accelerated aging at 40 ° C

- at (25 ± 2) ° C / (60 ± 5) relative humidity.

STABILITY STUDY TABLE

Content of p-aminophenol CO., LTD Does not contain and o Oh • »· • • • ► to · Ο Η g • • • • • 4 1 1 • » • • • « 1 1 • CQ Ο 5? ID -Η ο Г © hh and MS, • «» In the village A 4 1 4 • • • • 1 • · in • in * 1 1 • 1 9 » a 4 1 • in • • 1 • · • 4 Propyl parahydroxybenzoate [mg / 100 tnl] CM 20.9 19,2 21.2 20,0 19,0 18.9 I 20,3 | 20,4 18,8 | 04 00 19,0 Methyl parahydroxybenzoate [mg / 100 ml] 102,7 1 94,9 99,2 101,4 1 1 94.9 I 93,8 | 100,5 I oh oh oh 99,4 I 90.5 I 90,4 Sorbitol [g / 100 ml] o 30,500 30,400 Ο ο 40 θ 'CO 30,202 th most common , 30,401 I 30,503 th most common 30,300 1 Fr. 40 o 'm 30,404 | o o sp o 'm 30,330 Paracetamol 1 [g / 100 ml] Oh 3,360 3,395 th most common 3,381 th most common 3,362% 3,367 th most common 6D £ '£ 3,393 th most common 3,362 th most common 3,389 th most common 3,374 th most common 3,379 th most common Dextromethorphan hydrobromide [mg / 100 ml] 00 99.0 Ο o 'ο <ο ο 99,2 98.0 o o 'o 99.1 100,5 1 D98.7 99.0 98.5 Chlorpheniram in maleate [mg / 100 ml] wo cn 13,4 Ο it 13.5 WHAT JV 13.5 p 13.5 tG magazine 40 magazine en cn 13.3 Pseudoephedrine hydrochloride [g / 100 ml] 4D 0,200 1,202 th most common 0.201 0,199 0,198 0.201 .202 0,200 0,200 0,199 0,199 Reaction to solution (pH) m 5.0 ι / Ί 5.0 1 5.2 Ι / Ί sch «Mr. 5.0 5.0 1P 5.0 1 5,0] The smell Tf cherry specific Ο 3 ο ι 1 1 1 1 1 L 1 1 1 1 1 1 1 i L Color CO., LTD deep red ο S ο 1 1 1 i 1 t 1 1 1 1 l 1 Appearance MS clear viscous liquid hand 1 > 1 1 1 1— 1 1— 1 1— 1 1 1 1— Storage conditions and time Initial analysis X χ ο ο S X et Ο 00 270 days 1 3 months 6 months Nine months 12 months 18 months 24 months 36 months

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Claims (1)

Patent Claims 1. Liquid dosage form for oral administration of a combination drug comprising acetaminophen (paracetamol), chlorophenyramine maleate, dextromethorphan hydrobromide and pseudoephedrine hydrochloride comprising polyethylene glycol, polyvinylpyrrolidone, aromatizin, saccharin, aromatizin, saccharin, aromatin containing a mixed solvent consisting of propylene glycol, polyethylene glycol 400 and ethanol 96% in a ratio of 1: 1 to 4: 0.5 to 2; pH 5.0 ± 0.5 buffer of sodium citrate and citric acid; disodium edetate from 0.01 to 0.05 w / v %; polyvinylpyrrolidone from 0.01 to 1.5 w / v %; sorbitol from 10.0 to 40.0 w / v %; saccharin sodium from 0.05 to 0.30 w / v %.