Pharmaceutical composition comprising benzocaine with enhanced stability

A technology of benzocaine and stabilizer, applied in the field of pharmaceutical compositions, can solve the problems such as undesired synthesis of benzocaine derivatives

Inactive Publication Date: 2019-06-04
MEDICE ARZNEIMITTEL PUTTER
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The present inventors have found that during storage of formulations comprising benzocaine and sugar, benzocaine may react with sugar (such as glucose) via the Maillard reaction, resulting in undesirable benzocaine Derivative synthesis

Method used

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  • Pharmaceutical composition comprising benzocaine with enhanced stability
  • Pharmaceutical composition comprising benzocaine with enhanced stability

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] Embodiment 1: preparation preparation

[0069] Four different tablet formulations were produced using the following ingredients:

[0070] Element

[g] Ingredients per 1000g

Sodium carboxymethyl cellulose

10.0

peppermint

5.0

Povidone K 25

10.0

Type III Sucrose Stearate

20.0

Sodium Saccharinx 2 H2O

1.0

talc

79.9

L-Lysine Monohydrate

0 / 1.5 / 3.0 / 10.0

Sorbitol

872.7 / 870.7 / 869,2.7 / 859.2

Benzocaine

1.9

sum

1000g

[0071] Tablets of 1000 mg each are provided with the stated ingredients using the following method:

[0072] Sodium saccharin, benzocaine and povidone K25 were dissolved in 96% ethanol at room temperature to obtain drug solution 1.

[0073] Drug solution 1 was sprayed onto about 50% sorbitol in a fluidized bed system, and dried at 25-35° C. until ethanol evaporated to obtain dry material 1 .

[0074] The dry mass 1 was mixed with the remaining appro...

Embodiment 2

[0078] Embodiment 2: Analytical method

[0079] Analysis was performed using high pressure liquid chromatography (HPLC) according to Ph. Eur. 2.2.29.

[0080] The separation column is Kinetex C18, 150mm x 4.6mm. Eluent A was 20 mM sodium acetate in water, pH adjusted to 4.7 with acetic acid. Eluent B is acetonitrile. The applied gradient starts at 14 vol.-% eluent B and ends at 80 vol.% eluent B at a rate of about 1 ml / min. The injection volume was 15 μl.

[0081] Analysis was performed at 8°C by UV detection at 288nm and reference 400nm.

[0082] 0.5 g of the tablet of Example 1 was thoroughly dissolved in 50 ml of 25% acetonitrile. The control was a solution of 1.5 mg benzocaine in 100 ml 25% acetonitrile.

[0083] This control showed a peak at an elution volume of approximately 19 ml, which was determined to be undegraded benzocaine. Samples stored for 1 month showed additional peaks (B1 to B12) between elution volumes of 6.5 ml and 13 ml, with a distinct peak at 7.5...

Embodiment 3

[0084] Example 3: Results

[0085]

[0086] It was found that the presence of L-lysine monohydrate in a quantitative manner prevented the formation of impurities B1 to B12, especially of impurity B4, which was thought to represent the Maillard product of benzocaine with glucose.

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PUM

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Abstract

The invention provides a pharmaceutical composition comprising benzocaine with enhanced stability. Disclosed is a pharmaceutical formulation comprising benzocaine, a pharmaceutically acceptable salt or derivative thereof as a pharmaceutically active agent comprising at least one nucleophilic amino group, a reducing sugar, an excipient, and an amino acid as a stabilizing agent with at least one free amino group, wherein the stabilizing agent reacts with the reducing sugar in order to at least substantially reduce the Maillard reaction between the at least one nucleophilic amino group of the pharmaceutically active agent with the reducing sugar.

Description

[0001] The present invention relates to a pharmaceutical composition comprising at least benzocaine as pharmaceutically active agent. Background technique [0002] Benzocaine is a local anesthetic commonly used as a topical pain reliever or in cough drops. It is the active ingredient in many over-the-counter numbing creams, such as those used for mouth sores. Pain is caused by stimulation of free nerve endings. When this nerve terminal is stimulated, sodium enters the neuron, causing nerve depolarization and subsequent action potential firing. The action potential travels down the nerve toward the central nervous system, which interprets this propagation as pain. Benzocaine acts to inhibit voltage-dependent sodium channels (VDSCs) on neuronal membranes, thereby halting the propagation of action potentials. [0003] Benzocaine is often formulated with various other compounds. Typically the formulations will contain a sugar, such as glucose, either intentionally or unintenti...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/20A61K47/18A61K47/26A61K31/439A61P23/02A61P27/16A61P29/00
CPCA61K9/2013A61K9/2018A61K31/245A61K47/18
Inventor 理查德·阿默尔乌维·鲍勃
Owner MEDICE ARZNEIMITTEL PUTTER
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