Pharmaceutical-Grade Ferric Citrate Manufacturing Process

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Solution Overview

Problem

There is a need for a scalable and consistent manufacturing process to produce pharmaceutical-grade ferric citrate that meets established standards for quality and pharmaceutical use, particularly for treating hyperphosphatemia and metabolic acidosis in humans.

Innovation Solution

A method involving the steps of dissolving ferric chloride hexahydrate and sodium hydroxide, forming a ferric hydroxide precipitate, washing and suspending it, adding citric acid to form a ferric-organic acid solution, and then isolating and drying the ferric citrate, ensuring compliance with release specifications through quality control measures.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a manufacturing process is developed to produce ferric citrate, then the compound can be used to treat hyperphosphatemia and metabolic acidosis, but the process must ensure pharmaceutical-grade quality consistency and compliance with release specifications

Engineering Contradiction:

Improvequality consistencyVSAvoidmanufacturing process complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The manufacturing process is divided into distinct sequential steps: dissolving ferric chloride hexahydrate and sodium hydroxide, forming ferric hydroxide precipitate, washing and suspending, adding citric acid, and isolating and drying ferric citrate. Each step includes specific quality control measures to ensure pharmaceutical-grade consistency while maintaining manageable process complexity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The process controls critical parameters including pH levels during precipitation and dissolution, temperature during heating and drying, and concentrations of reactants. These parameter changes ensure consistent pharmaceutical-grade quality while providing clear guidance for manufacturing compliance.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If ferric citrate is produced for large-scale manufacturing, then productivity increases, but maintaining pharmaceutical-grade quality standards becomes more challenging

Engineering Contradiction:

Improvemanufacturing scaleVSAvoidquality compliance

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The process includes preliminary quality control measures at each manufacturing step, such as controlling pH during precipitation, washing the precipitate to remove impurities, and maintaining specific temperature ranges during drying. These preliminary actions ensure quality compliance is built into the process from the beginning, enabling large-scale production without sacrificing pharmaceutical-grade standards.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The manufacturing process incorporates quality control checkpoints that monitor critical parameters and provide feedback for adjustments. This ensures consistent pharmaceutical-grade quality even during large-scale production by allowing real-time corrections to maintain compliance with release specifications.

Inventive Principle:

Principle #23Feedback

3Reliability

If ferric citrate is used to treat hyperphosphatemia, then phosphate binding occurs in the gastrointestinal tract, but gastrointestinal adverse effects may occur

Engineering Contradiction:

Improvetreatment efficacyVSAvoidgastrointestinal adverse effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent acknowledges that ferric citrate can cause gastrointestinal adverse effects as a known challenge. The pharmaceutical-grade manufacturing process ensures high purity and consistency, which helps minimize these adverse effects while maintaining effective phosphate binding in the gastrointestinal tract for treating hyperphosphatemia.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

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

The process enables the production of pharmaceutical-grade ferric citrate suitable for large-scale manufacturing, effectively treating hyperphosphatemia and metabolic acidosis with reduced gastrointestinal adverse effects compared to chemical-grade formulations.

Implementation Method 1

forming a ferric hydroxide precipitate

Methodology Applied

Scientific EffectPrecipitation: Precipitation

Implementation Method 2

adding citric acid to form a ferric-organic acid solution

Methodology Applied

Scientific EffectChemical Bonding: Chemical Bonding

Implementation Method 3

isolating and drying the ferric citrate

Methodology Applied

Scientific EffectEvaporation: Evaporation

Data Source

PatentUS8093423B2Pharmaceutical-grade ferric organic compounds, uses thereof and method of making same

Publication Date: 2012.01.10 PANION & BF BIOTECH INC

AI summary

The present invention discloses a pharmaceutical-grade ferric organic compounds, including ferric citrate, which are soluble over a wider range of pH, and which have a large active surface area. A manufacturing and quality control process for making a pharmaceutical-grade ferric citrate that consistently complies with the established Manufacture Release Specification is also disclosed. The pharmaceutical-grade ferric organic compounds are suitable for treating disorders characterized by elevated serum phosphate levels.