Azacitidine Injection Preparation Removing Activated Carbon

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Solution Overview

Problem

The existing methods for preparing azacitidine for injection face challenges such as the need for activated carbon, which poses safety risks and increases production complexity, and require high energy consumption due to temperature control issues, affecting product stability and efficiency.

Innovation Solution

A method that eliminates the use of activated carbon by controlling bacterial endotoxin levels and maintaining the azacitidine solution temperature between 2-6°C, specifically 4-6°C, to enhance stability and efficiency, involving steps like measuring water for injection, adding mannitol and azacitidine, filtration, freeze-drying, and nitrogen filling.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If activated carbon is added to remove pyrogen, then bacterial endotoxin levels are reduced, but production complexity and safety risks increase due to filtration requirements

Engineering Contradiction:
Improvebacterial endotoxin controlVSAvoidproduction process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention extracts and removes the activated carbon step from the preparation process entirely. By controlling the quality of raw materials and excipients to have low bacterial endotoxin levels from the source, the patent eliminates the need for the activated carbon adsorption and filtration steps, thereby reducing production complexity while maintaining reliability

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention applies preliminary action by pre-controlling the bacterial endotoxin levels in raw materials and excipients before the preparation process begins. This preventive approach ensures that the starting materials already meet the required purity standards, eliminating the need for subsequent purification steps with activated carbon

Inventive Principle:
Principle #10Preliminary action

2Stability of the object's composition

If temperature is controlled at 2-6°C to enhance stability, then product quality is improved, but energy consumption increases

Engineering Contradiction:
Improveazacitidine solution stabilityVSAvoidenergy consumption
Core Design Contradiction:
Stability of the object's compositionVSUse of energy by moving object

Solution Approach 1:

The invention applies parameter changes by optimizing the temperature range to 2-6°C, which is a specific parameter adjustment that balances stability enhancement with energy consumption considerations. This temperature parameter change ensures azacitidine stability while being more energy-efficient than lower temperature approaches

Inventive Principle:
Principle #35Parameter changes

3Reliability

If activated carbon filtration is performed, then pyrogen removal is achieved, but activated carbon leakage and residue problems occur

Engineering Contradiction:
Improvepyrogen removal efficiencyVSAvoidactivated carbon leakage and residue
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and eliminates the activated carbon filtration step from the process. By pre-controlling bacterial endotoxin levels in raw materials, the patent removes the need for activated carbon entirely, thereby eliminating both the pyrogen removal function and the harmful side effects of carbon leakage and residue

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces the reusable activated carbon material with a strategy based on controlling raw material quality. This approach uses disposable, controlled-quality materials from the start rather than introducing a secondary purification agent that requires removal, eliminating residue problems

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

4Temperature

If circulating condensed water is used for cooling, then cooling efficiency is improved, but production safety risks increase due to flammability concerns

Engineering Contradiction:
Improvecooling efficiencyVSAvoidflammability and explosion risk
Core Design Contradiction:
TemperatureVSObject-affected harmful factors

Solution Approach 1:

The invention applies the inert environment principle by using water-based cooling systems instead of flammable solvents. Water creates a safe, non-flammable cooling environment that maintains cooling efficiency while eliminating fire and explosion hazards associated with organic solvents

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach simplifies the production process, reduces energy consumption, and ensures stable product quality with reduced bacterial endotoxin levels, making it more suitable for commercial production and improving the safety and efficacy of azacitidine for injection.

Implementation Method 1

adding mannitol and stirring to dissolve

Methodology Applied
Scientific EffectSolvation: Solvation

Implementation Method 2

adding azacitidine with the desired quality and stirring the mixture to form a solution

Methodology Applied
Scientific EffectSolvation: Solvation

Implementation Method 3

freeze-drying at a preset temperature

Methodology Applied
Scientific EffectFreeze-drying: Freeze Drying

Data Source

PatentUS10617649B2Preparation method of azacitidine for injection
Publication Date: 2020.04.14 ZHEJIANG HUAHAI PHARMACEUTICAL CO LTD

AI summary

Disclosed is a preparation method for an azacitidine for injection, wherein each injection vial of azacitidine for injection contains 100 mg of azacitidine and 100 mg of mannitol. The preparation method comprises the steps of measuring 80% of the total volume of water for injection at a temperature of 2-6° C.; adding mannitol, and stirring to completely dissolved at a temperature of 2-6° C.; adding azacitidine, stirring to completely dissolved at a temperature of 2-6° C. to obtain an azacitidine solution for injection; filling each injection vial with 23 ml azacitidine solution for injection after filtration; freeze-drying at a preset temperature; and stoppering, capping and packaging after nitrogen filling. The preparation method has the advantages of a simple process, low energy consumption, high production efficiency and stable product quality.