Pharmaceutical Granule Homogeneity via Spray Coating and Drying

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Solution Overview

Problem

The existing manufacturing process for PICOLAX™, a pharmaceutical product, faces issues with inhomogeneity in final and intermediate products due to low binding properties between citric acid and magnesium oxide, leading to extra processing time, economic losses, and dust production, along with physical degradation of potassium bicarbonate during mixing.

Innovation Solution

A process involving the use of a multi-dimension blender for dry mixing citric acid and magnesium oxide, and spraying a sodium picosulphate solution onto potassium bicarbonate, followed by drying, to create homogeneous granules with a coated layer structure, reducing processing time and improving homogeneity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If conventional mixing processes are used to blend citric acid and magnesium oxide, then the mixing operation can be completed, but inhomogeneity arises in granule size and distribution due to low binding properties between particles

Engineering Contradiction:
Improvemixing operationVSAvoidgranule size homogeneity
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

A binding agent is introduced as an intermediary substance to facilitate adhesion between citric acid and magnesium oxide particles during mixing. This mediator overcomes the low binding properties between the two main ingredients, enabling them to form homogeneous granules with consistent size distribution without excessive dust generation or material loss.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If extra magnesium oxide is added to compensate for losses during blending, then mixing losses are covered, but economic losses increase and processing time extends

Engineering Contradiction:
Improvemixing process completenessVSAvoidproduction efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The conventional mechanical mixing system is replaced or supplemented with a granulation process that uses binding agents to create cohesive granules. This substitution prevents material loss during handling and transfer operations, eliminating the need for overage additions and reducing both economic losses and processing time associated with compensating for mixing inefficiencies.

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

3Ease of manufacture

If conventional mixing is used for potassium bicarbonate and sodium picosulphate, then blending occurs, but physical degradation and dissolution of particles happen during the process

Engineering Contradiction:
Improveblending operationVSAvoidparticle integrity
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The ingredients are pre-granulated with binding agents before final mixing, creating robust granule structures that resist physical degradation during subsequent handling and processing. This preliminary granulation action protects particle integrity throughout the manufacturing process, preventing dissolution and smashing that would otherwise occur during conventional blending operations.

Inventive Principle:
Principle #10Preliminary action

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 new process achieves significant reduction in processing time, enhances product homogeneity, minimizes dust and contamination, and ensures uniformity of active substance content, resulting in a more efficient and reproducible final product.

Implementation Method 1

spraying a sodium picosulphate solution onto potassium bicarbonate

Methodology Applied
Scientific EffectSpray: Spray

Implementation Method 2

drying, to create homogeneous granules with a coated layer structure

Methodology Applied
Scientific EffectEvaporation: Evaporation

Data Source

PatentEP2207526B1Process for the manufacure of a pharmaceutical product comprising citric acid, magnesium oxide, potassium bicarbonate and sodium picosulfate, pharmaceutical composition comprising granules obtained by such process and intermediate products thereof
Publication Date: 2017.11.22 FERRING INT CENT SA
  • EP2207526B1 patent drawingFigure 1
  • EP2207526B1 patent drawingFigure 2

AI summary

A process for the preparation of a pharmaceutical composition comprising a homogeneous or substantially homogeneous mixture of citric acid, magnesium oxide, potassium bicarbonate and sodium picosulphate and, optionally, saccharin sodium and/or orange flavour; products, intermediate products, and uses thereof.