Dried Granulate Particle Size Control via Moisture-Adjusted Milling

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Solution Overview

Problem

Current methods for producing wet granulates with desirable particle size distribution and reduced fines content are challenging, as they often result in either larger particle sizes or wider distributions, and are difficult to control precisely, especially in achieving small average particle sizes with narrow distributions.

Innovation Solution

A method involving drying a wet granulate to a predetermined relative moisture content, followed by milling and further drying to achieve a final dried granulate with specific particle size ranges and distribution, utilizing techniques such as partial drying and spherinization to facilitate processing through small screens without clogging and minimize fines.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Area of stationary object

If wet granulation is used to increase particle size, then surface area decreases for taste masking, but particle size distribution becomes wide and control precision deteriorates

Engineering Contradiction:
Improvesurface areaVSAvoidparticle size distribution
Core Design Contradiction:
Area of stationary objectVSManufacturing precision

Solution Approach 1:

The granulation process is segmented into multiple stages: initial wet granulation to form core particles, followed by sequential coating layers. Each stage controls particle size independently, allowing precise final distribution while achieving adequate surface area reduction for taste masking.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The core particles are pre-formed with controlled size distribution before coating is applied. This preliminary action establishes a foundation that prevents excessive size variation in the final product, as the coating adds uniform thickness to already-sorted cores.

Inventive Principle:
Principle #10Preliminary action

2Length of moving object

If milling is used to reduce average particle size, then surface area increases, but fines content increases and particle size distribution widens

Engineering Contradiction:
Improveaverage particle sizeVSAvoidfines content
Core Design Contradiction:
Length of moving objectVSObject-generated harmful factors

Solution Approach 1:

Particles are pre-classified into size ranges before the final granulation step. This preliminary sorting ensures that only particles within the target size range undergo further processing, preventing the generation of excessive fines that would occur with aggressive milling of mixed-size materials.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The granulation parameters (liquid-to-powder ratio, binding agent concentration, mixing time) are specifically adjusted based on the pre-sorted particle size distribution. This parameter optimization minimizes particle breakage and fines generation while achieving the desired average size, eliminating the need for aggressive milling.

Inventive Principle:
Principle #35Parameter changes

3Length of moving object

If small screens are used during milling to obtain small particle sizes, then average particle size decreases, but screen clogging occurs and productivity decreases

Engineering Contradiction:
Improveparticle sizeVSAvoidthroughput
Core Design Contradiction:
Length of moving objectVSProductivity

Solution Approach 1:

Materials are pre-dried to optimal moisture content before screening. This preliminary moisture control prevents material from adhering to screen surfaces, eliminating clogging issues that would force the use of larger screens and subsequent size reduction steps.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

Screening is performed at controlled moisture levels and with optimized screen geometry (opening size, mesh pattern) matched to the pre-sorted particle distribution. This parameter matching allows small effective screen openings without clogging, maintaining high throughput while achieving small particle sizes.

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

The method effectively produces granulates with average particle sizes between 150 and 600 microns and no more than 40% of particles smaller than 105 microns, achieving a narrow particle size distribution and reducing fines content, which is crucial for pharmaceutical applications like taste masking and controlled release coatings.

Implementation Method 1

drying a wet granulate having an initial moisture content to a predetermined first relative moisture content to form a partially dried wet granulate

Methodology Applied
Scientific EffectEvaporation: Evaporation

Implementation Method 2

milling the partially dried wet granulate to obtain a milled partially dried wet granulate having predetermined average particle size and/or particle size distribution

Methodology Applied
Scientific EffectMechanical force: Mechanical Force

Implementation Method 3

drying the milled partially dried wet granulate to produce a final dried wet granulate

Methodology Applied
Scientific EffectEvaporation: Evaporation

Data Source

PatentEP2359811B1Dried milled granulate and methods
Publication Date: 2012.11.14 CIMA LABS INC

AI summary

The present invention relates to a dried wet granulate having a desirable average particle size and particle size distribution and dosage forms made from that granulate.