Iron Sucrose Complex Preparation via pH-Controlled Precipitation

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Solution Overview

Problem

Existing methods for producing iron sucrose are costly, inefficient, and fail to meet regulatory molecular weight specifications, often involving expensive freeze drying, lengthy intermediary steps, and potential contamination or incomplete conversion issues.

Innovation Solution

A cost-effective method involving the reaction of a ferric salt solution with an inorganic base at pH 3.5 to 7.0 to form ferric oxyhydroxide, which is then treated with sucrose at 20-100°C and pH 8.0 to 13.0, followed by partial concentration and precipitation using an organic solvent to isolate the iron sucrose complex within the desired molecular weight range of 34,000 to 60,000 daltons.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If freeze drying is used to obtain iron sucrose complex, then the product purity is improved, but the manufacturing cost increases significantly

Engineering Contradiction:

Improveproduct purityVSAvoidmanufacturing cost

Core Design Contradiction:

Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent changes the physical state parameters by using spray drying instead of freeze drying, and optimizes temperature parameters during concentration and drying processes to achieve product purification without the high costs associated with freeze drying technology

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs conventional, cost-effective drying equipment and reagents rather than expensive specialized freeze drying equipment, using readily available materials to achieve the desired product quality at lower manufacturing costs

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

2Reliability

If calcium-sugar complex is used as intermediary in iron-sugar complex preparation, then the reaction pathway is established, but the process length and complexity increase

Engineering Contradiction:

Improvereaction pathway establishmentVSAvoidprocess length

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent removes the unnecessary intermediary calcium-sugar complex step from the synthesis pathway, directly reacting iron salts with sucrose to form the iron-sugar complex, thereby simplifying the process while maintaining reaction reliability

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent divides the synthesis into optimized discrete stages: pH adjustment to form ferric oxyhydroxide, followed by direct complexation with sucrose at controlled pH and temperature, eliminating redundant intermediate steps

Inventive Principle:

Principle #1Segmentation

3Stability of the object's composition

If pH 6.5 to 7.5 is used for saccharin iron oxide preparation, then the pH condition is optimized, but no formation of saccharin iron oxide occurs

Engineering Contradiction:

ImprovepH optimizationVSAvoidproduct formation

Core Design Contradiction:

Stability of the object's compositionVSManufacturing precision

Solution Approach 1:

The patent systematically varies pH parameters across different synthesis stages, establishing pH 3.5-7.0 for ferric oxyhydroxide formation and pH 8.0-13.0 for complexation with sucrose, thereby achieving product formation that fails at pH 6.5-7.5

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent dynamically adjusts pH conditions at different stages of the reaction process rather than maintaining a static pH, allowing optimal conditions for each specific chemical transformation step

Inventive Principle:

Principle #15Dynamics

4Ease of operation

If inorganic bases like ammonium hydroxide or sodium hydroxide are used for ferric oxyhydroxide preparation, then the base selection is simplified, but the desired complex formation fails

Engineering Contradiction:

Improvebase selection simplicityVSAvoidcomplex formation success

Core Design Contradiction:

Ease of operationVSManufacturing precision

Solution Approach 1:

The patent identifies and applies the critical parameter of base selection, specifically using potassium hydroxide or cesium hydroxide instead of conventional bases, which fundamentally changes the reaction outcome to achieve successful complex formation

Inventive Principle:

Principle #35Parameter changes

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 method produces a pure, cost-effective iron sucrose complex that meets regulatory specifications, is pH and heat stable, and can be used as an injectable or formulated in various pharmaceutical forms, overcoming the limitations of previous methods.

Implementation Method 1

reaction of a ferric salt solution with an inorganic base at pH 3.5 to 7.0 to form ferric oxyhydroxide

Methodology Applied

Scientific EffectPrecipitation: Precipitation

Implementation Method 2

treated with sucrose at 20-100°C and pH 8.0 to 13.0 to give iron sucrose complex

Methodology Applied

Scientific EffectComplexation: Chemical Bonding

Implementation Method 3

precipitation, by addition of an organic solvent or mixture thereof to give iron sucrose complex in sucrose

Methodology Applied

Scientific EffectPrecipitation: Precipitation

Data Source

PatentUS8030480B2Cost-effective process for preparation of manufacture of iron sucrose

Publication Date: 2011.10.04 EMCURE PHARMACEUTICALS LTD

AI summary

The present invention relates to a cost-effective process for manufacture of iron sucrose complex.