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Method for controlling genotoxic impurities in metformin hydrochloride sustained release tablet preparation process

A metformin hydrochloride and genotoxic technology, which is applied in the direction of making medicines into special physical or taking forms of devices, pill delivery, pharmaceutical formulations, etc. The effect of strong operability and simple control method

Inactive Publication Date: 2021-07-09
SHANDONG INST FOR FOOD & DRUG CONTROL +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] At present, domestic and foreign studies on genotoxic impurities in metformin hydrochloride sustained-release tablets N - Research on nitrosodimethylamine, mostly focused on N - Analysis and detection of nitrosodimethylamine content, and how to use it in the preparation process N -Nitrosodimethylamine is controlled at a low level, and no public reports have been seen

Method used

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  • Method for controlling genotoxic impurities in metformin hydrochloride sustained release tablet preparation process
  • Method for controlling genotoxic impurities in metformin hydrochloride sustained release tablet preparation process
  • Method for controlling genotoxic impurities in metformin hydrochloride sustained release tablet preparation process

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Example 1 Investigation of Key Prescription Factors in Preparation Technology

[0022] Preliminary studies have found that no genotoxic impurities were detected in metformin hydrochloride API and various excipients N -Nitrosodimethylamine, and does not generate impurities under acid, alkali, oxidative degradation conditions N -Nitrosodimethylamine, so we conduct a compatibility study of raw materials and excipients to investigate the influence of prescription factors in the preparation process. N - The content determination of nitrosodimethylamine adopts the analytical method of GC-MS. The results are shown in Table 1.

[0023] Table 1 Compatibility study results of raw materials and excipients

[0024]

[0025] The research results showed that: ① the same batch of raw materials, the higher the nitrite content of hypromellose in the mixed powder of excipients, the higher the content of hypromellose in the sample N - The higher the content of nitrosodimethylamine;...

Embodiment 2

[0027] Example 2 The formulation of the limit of impurity dimethylamine content in metformin hydrochloride crude drug

[0028] 1. Sample Preparation

[0029] According to the proportion of the prescription, the metformin hydrochloride bulk drug with different dimethylamine content and the sustained-release matrix material hypromellose K100M, microcrystalline cellulose and sodium carboxymethylcellulose were placed in a high-efficiency wet granulator and mixed for 5- Mix for 10 minutes, then add 20% ethanol solution to prepare wet granules; wet granules are boiled and dried in a fluidized bed below 40°C (moisture ≤ 2.0%), dry granules are granulated with a 20-mesh oscillating granulator, and finally granulated The granules after granulation are uniformly mixed with magnesium stearate and hypromellose K100M in a mixer, and compressed into tablets. Simultaneously carry out research on influencing factors to investigate the impact of dimethylamine content in raw materials on produ...

Embodiment 3

[0034] Embodiment 3 Limit formulation of impurity nitrite content in the auxiliary material hypromellose

[0035] 1. Sample Preparation

[0036] According to the proportion of the prescription, the metformin hydrochloride bulk drug and the slow-release matrix material hypromellose K100M, microcrystalline cellulose, and sodium carboxymethylcellulose with different nitrite contents were placed in a high-efficiency wet granulator and mixed for 5- Mix for 10 minutes, then add 20% ethanol solution to prepare wet granules; wet granules are boiled and dried in a fluidized bed below 40°C (moisture ≤ 2.0%), dry granules are granulated with a 20-mesh oscillating granulator, and finally granulated The granules after granulation are uniformly mixed with magnesium stearate and hypromellose K100M in a mixer, and compressed into tablets. At the same time, the influence factor test was carried out to investigate the effect of the nitrite content in the auxiliary material hypromellose on the ...

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Abstract

The invention relates to the technical field of preparation processes, in particular to a method for controlling genotoxic impurities in a metformin hydrochloride sustained release tablet preparation process, which comprises the following steps of: controlling the content of impurity dimethylamine in a raw material medicine metformin hydrochloride and the content of impurity nitrite in an auxiliary material hydroxypropyl methylcellulose; effective control of the genotoxic impurity N-nitrosodimethylamine is achieved, side reactions of medication of patients are reduced, and medication safety of the patients is guaranteed to a certain extent; the content of the genetic toxic impurity N-nitrosodimethylamine of the metformin hydrochloride sustained-release tablet is far lower than that of the State Food and Drug Administration and an acceptable limit specified by FDA (Food and Drug Administration).

Description

technical field [0001] The invention relates to the technical field of preparation technology, in particular to a method for controlling genotoxic impurities in the preparation technology of metformin hydrochloride sustained-release tablets. The method controls the quality of raw materials and auxiliary materials to prepare genotoxic impurities N - High-quality metformin hydrochloride sustained-release tablets with nitrosodimethylamine content far below the acceptable limit stipulated by the State Drug Administration and FDA. Background technique [0002] Metformin hydrochloride (Metformin hydrochloride), the chemical name is 1,1-metformin hydrochloride, the molecular formula is C 4 h 11 N 5 HCl, its structural formula is: [0003] [0004] Metformin hydrochloride is a biguanide hypoglycemic drug. It is mainly used clinically for type II diabetes in adults whose simple diet control and physical exercise are ineffective. It is especially suitable for type II obesity dia...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/22A61K31/155A61K47/38A61P3/10A61J3/00
CPCA61J3/00A61K9/2054A61K31/155A61P3/10
Inventor 文松松陈俊亮徐玉文王维剑牛冲郭常川赵晓辉刘杰
Owner SHANDONG INST FOR FOOD & DRUG CONTROL
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