Injectable liquid formulation of paracetamol

A technology for paracetamol and injection, which can be used in non-central analgesics, medical preparations containing active ingredients, antipyretics, etc. Effect

Inactive Publication Date: 2006-03-22
T·源春
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The stable paracetamol injection in the prior art has the following disadvantages due to the toxicity of the antioxidants contained: it may cause irritation, allergies and / or carcinogenic effects in some patients
Therefore these solutions for injection should not be stored in plastic containers which are partially permeable to oxygen or contain traces of oxidative residues

Method used

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  • Injectable liquid formulation of paracetamol
  • Injectable liquid formulation of paracetamol

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] The preparation of embodiment 1 liquid pharmaceutical preparation of the present invention and the analysis of this preparation with high performance liquid chromatography

[0033] Formulations 001, 002, 003, 004, 005 and 006 were prepared by mixing paracetamol, ultrapure water for injection, optionally (formulation 004) propylene glycol, buffers (phosphate buffer, phosphate-citric acid salt buffer or citrate buffer) and isotonic agent (sodium chloride); the resulting mixture was heated at 70-90°C for about 15 minutes to avoid recrystallization of paracetamol due to the presence of crystallization nuclei; into a glass bottle, and sterilize the glass bottle at 121°C for 15 minutes.

[0034] According to the method recommended by the European Pharmacopoeia (European Pharmacopoeia 4.4, pp.3503-4, 04 / 2003: 0049Paracetamol), the preparation solution before and after sterilization is analyzed by high-performance liquid chromatography. The determination conditions of high-perf...

Embodiment 2 2

[0042] The research of embodiment 2 dimer formation conditions

[0043] 1) The influence of temperature and time

[0044] After preparation 001 in Example 1 was heated at 70-90° C. for 15 minutes and stored in a glass bottle, the influence of temperature on the formation of paracetamol dimer represented by structural formula (I) was investigated. This formulation was in turn stored at different temperatures and / or subjected to different sterilization times and analyzed by HPLC as described in Example 1.

[0045] The main results are shown in Table 2.

[0046] Paracetamol (%)

p-Aminophenol(%)

Dimer (%)

Store at 70°C for 1 hour (non-sterile)

100.8

not detected

not detected

Store at 60°C for 14 days (non-sterile)

100.2

not detected

0.10

Sterilize at 121°C for 10 minutes

99.9

not detected

0.09

Sterilize at 121°C for 20 minutes

99.7

not detected

0.18

After sterilizat...

Embodiment 3

[0051] Embodiment 3 stability study

[0052] After the 001 preparation in Example 1 was heated at 70-90°C for 15 minutes and packed in a glass bottle or a polypropylene infusion container, it was sterilized in a glass bottle at 121°C for 15 minutes or in a polypropylene container at 120°C. The stability was examined after sterilization at ℃ for 20 minutes.

[0053] With the high performance liquid chromatography analysis described in embodiment 1, the results are shown in Table 3.

[0054] 50ml glass bottle

100ml polypropylene container

start

state

10 months later

start

state

10 months later

25℃

40℃

25℃

40℃

Osmolality

(mOsm / kg)

283

288

285

281

289

283

Paracetamol content (%)

100.3

100.7

99.1

100.3

100.4

99.4

Dimer content (%)

0.11

0.23

0.73

0.09

0.14

0.47 ...

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Abstract

The invention relates to a novel injectable liquid formulation of paracetamol, comprising an aqueous solvent, a buffer agent with a pKa between 4.5 and 6.5, an isotonic agent and the dimer of paracetamol of formula (I), a method for preparation of said formulation and the use of said dimer for the stabilisation of a liquid paracetamol pharmaceutical formulation.

Description

technical field [0001] The invention relates to a novel paracetamol liquid medicine preparation for injection, which contains paracetamol dimer as an active ingredient, and relates to a preparation method of the preparation and an application of the dimer in stabilizing the paracetamol liquid preparation. Background technique [0002] Paracetamol (international non-proprietary drug name is paracetamol or N-(4-hydroxyphenyl)acetamide) is a widely used antipyretic and analgesic drug in clinical practice. There is an urgent need for a stable liquid pharmaceutical formulation of this active ingredient for injection administration, especially for intravenous infusion. [0003] It is known that paracetamol is easily hydrolyzed in aqueous solution to form p-aminophenol; and p-aminophenol itself is easily degraded into quinoneimine (quinoneimine) (see J.E.Fairbrother, "Acetaminophen" in Analytical Profiles of Drug Substances, 1974, vol.3, pp .1-109). The degradation rate of parace...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/167A61K9/08A61P29/00
CPCY10S514/97A61K31/167A61K9/08A61P29/00
Inventor T·源春
Owner T·源春
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