Amorphous Solid Dispersion Submicron Particle Control via Microfluidization

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current methods for producing amorphous solid dispersions struggle to control particle size in the submicron range while maintaining the amorphous nature of the solid dispersion particulates, often resulting in hollow particles or requiring additional processing steps like milling to achieve fine material.

Innovation Solution

A method utilizing microreaction technology for solvent-controlled co-precipitation, where a solution of a pharmaceutically active compound and a stabilizing agent is mixed with an anti-solvent in a microreactor, enabling the production of amorphous solid dispersions with particle sizes in the submicron range through microfluidization, which are stable and high-density.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If spray drying is used to produce solid dispersions, then particles are obtained, but they are hollow with low density and particle size in the range of 2-120 microns

Engineering Contradiction:

Improveparticle size controlVSAvoidparticle structure

Core Design Contradiction:

Manufacturing precisionVSShape

Solution Approach 1:

The invention changes the process parameters by using microfluidization technology with specific pressure (5-200 bar) and shear force conditions, along with controlled anti-solvent addition, to transform the particle formation mechanism from spray drying's hollow structure to dense submicron particles

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention replaces the thermal drying mechanism of spray drying with a mechanical microfluidization system that uses controlled shear forces and pressure to achieve particle formation and densification in a single step

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Shape

If hot melt extrusion is used to produce solid dispersions, then dense particles are obtained, but they have very coarse particles or pellets requiring additional downstream processing

Engineering Contradiction:

Improveparticle densityVSAvoidparticle size

Core Design Contradiction:

ShapeVSManufacturing precision

Solution Approach 1:

The invention segments the extrusion process into micro-scale fluidization units, dividing the coarse extrudate into submicron-sized particles through controlled shear forces and anti-solvent precipitation, eliminating the need for downstream milling

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention transitions from the one-dimensional extrusion process to a multi-dimensional microfluidization process that controls particle size in all three dimensions, achieving uniform submicron particles with high density

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

3Manufacturing precision

If conventional co-precipitation is used, then solid dispersions are obtained, but particle size control in the submicron range is difficult

Engineering Contradiction:

Improveparticle sizeVSAvoidprocess control

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The invention implements feedback control through controlled anti-solvent addition rates and microfluidization parameters that respond to mixing conditions, enabling precise particle size control in the submicron range while maintaining process simplicity

Inventive Principle:

Principle #23Feedback

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 allows for the production of amorphous solid dispersions with consistent particle size in the submicron range, maintaining the amorphous state and achieving high density, thereby enhancing bioavailability by improving dissolution kinetics and supersaturation.

Implementation Method 1

A method of producing amorphous solid dispersions by performing solvent controlled co-precipitation in an apparatus that facilitates molecular contact/interaction within a defined reaction chamber or micro channel

Methodology Applied

Scientific EffectCo-precipitation: Coprecipitation

Implementation Method 2

mixing the solutions with a second solvent which comprises at least one anti-solvent by means of microfluidization or a microreaction to obtain a suspension of amorphous particles by co-precipitation

Methodology Applied

Scientific EffectPrecipitation: Precipitation

Implementation Method 3

mixing the solutions with a second solvent which comprises at least one anti-solvent by means of microfluidization or a microreaction

Methodology Applied

Scientific EffectMicrofluidization:

Implementation Method 4

mixing the solutions with a second solvent which comprises at least one anti-solvent by means of microfluidization or a microreaction to obtain a suspension of amorphous particles by co-precipitation

Methodology Applied

Scientific EffectAnti-solvent effect:

Data Source

PatentUS20170209372A1A Method of Preparing Amorphous Solid Dispersion in Submicron Range by Co-Precipitation

Publication Date: 2017.07.27 HOVIONE HLDG LTD

AI summary

The present invention discloses a method for producing amorphous solid dispersions in a nanoparticulate form, through solvent controlled co-precipitation, using microfluidization/microreaction technology to promote high energy mixing/interaction at a micro and/or molecular level between the streams involved in the process. Feed streams, solvent and anti-solvent, are fed to an intensifier pump at individually controlled rates and forced to interact to micro- and/or nano-scale within a microreactor. The present invention also discloses amorphous solid dispersions obtained by the method of the invention as well as pharmaceutical compositions containing the same.