Calcium Acetate Granules Fluidized Bed Stability

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Solution Overview

Problem

Current phosphate binders for treating hyperphosphatemia and hypercalcemia associated with renal insufficiency have chemical instability, poor reproducibility, and inadequate particle size control, leading to ineffective treatment and safety concerns due to aluminum-based compounds and insufficient efficacy of sevelamer hydrochloride, while combination preparations with calcium acetate and magnesium carbonate suffer from decomposition issues.

Innovation Solution

A process using fluidized bed granulation to produce particulate calcium acetate granules, which are then mixed with magnesium salt components to create a stable and reproducible composition, enhancing chemical stability, storage life, and active ingredient release profile.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If tray drying is used to produce calcium acetate granules, then the manufacturing process is simple, but the chemical stability is poor and decomposition occurs

Engineering Contradiction:
Improvemanufacturing process simplicityVSAvoidchemical stability
Core Design Contradiction:
Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The patent changes the manufacturing parameters from tray drying to fluidized bed granulation, which controls particle formation and drying more effectively. This prevents decomposition while maintaining manufacturing feasibility through standardized process parameters

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces the mechanical tray drying system with a fluidized bed system that uses fluid dynamics to achieve uniform particle coating and drying. This substitution prevents hot spots and decomposition while maintaining ease of manufacture through automated control

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Ease of manufacture

If tray drying is used to produce calcium acetate granules, then the manufacturing process is straightforward, but the reproducibility is poor and particle size control is inadequate

Engineering Contradiction:
Improvemanufacturing process straightforwardnessVSAvoidparticle size control
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent changes the granulation process parameters by implementing fluidized bed technology with controlled fluidization velocity, spray rate, and particle residence time. These parameter changes enable precise particle size control while maintaining manufacturing straightforwardness through automated process control

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements feedback control in the fluidized bed granulation process, where particle size distribution is monitored and process parameters are adjusted accordingly. This ensures reproducible particle size control while maintaining ease of manufacture through self-regulating process dynamics

Inventive Principle:
Principle #23Feedback

3Reliability

If combination preparations of calcium acetate and magnesium carbonate are used, then the treatment efficacy is improved, but decomposition issues arise reducing stability

Engineering Contradiction:
Improvetreatment efficacyVSAvoidcompositional stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent segments the combination preparation into separately granulated calcium acetate and magnesium carbonate components that are mixed only in the final formulation stage. This segmentation prevents premature decomposition while maintaining treatment efficacy by preserving the chemical integrity of each active ingredient

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent extracts the decomposition problem by separating the calcium acetate and magnesium carbonate manufacturing processes. Each component is produced and stabilized independently through fluidized bed granulation, then combined in controlled proportions to form the final stable formulation

Inventive Principle:
Principle #2Taking out (Extraction)

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 results in a composition with improved chemical stability, enhanced storage stability, and optimized active ingredient release, effectively treating hyperphosphatemia and hypercalcemia with increased bulk density and flowability, reducing the risk of side effects and improving treatment efficacy.

Implementation Method 1

A process using fluidized bed granulation to produce particulate calcium acetate granules

Methodology Applied
Scientific EffectFluidized bed granulation: Fluidisation

Data Source

PatentEP2161022B1Production of phosphate connectors and phosphate connectors produced according to the method
Publication Date: 2012.10.10 MARIA CLEMENTINE MARTIN KLOSTERFRAU VERTRIEB GESELLSCHAFT MBH

AI summary

Preparing a composition, preferably a medicament, comprising a combination of calcium acetate and magnesium salts, comprises: (a) providing particulate calcium acetate granulate, which is produced by fluidized bed granulation; (b) providing a particulate magnesium salt component; (c) producing a mixture using the calcium acetate granulate and the magnesium salt component; and (d) processing the produced mixture to an administrable product, preferably orally administrable formulation, preferably medicament form. Independent claims are included for: (1) the composition, preferably medicament, obtained by the above process; (2) a process for producing particulate calcium acetate, in which the calcium acetate is produced in the form of calcium acetate granulates by fluidized bed granulation; and (3) a particulate calcium acetate, obtained in the form of calcium acetate granulate using fluidized bed granulation. ACTIVITY : Nephrotropic; Metabolic; Cardiovascular-Gen.; CNS-Gen.; Gastrointestinal-Gen. MECHANISM OF ACTION : None given.