Active Ingredient Particle Production via Solvent Precipitation

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing methods for producing therapeutic particles, such as nanoparticles and microparticles, often result in particles that are not uniform in size and solubility, affecting their stability and pharmacokinetics, particularly for active ingredients like paliperidone palmitate and ascorbic acid.

Innovation Solution

A method involving the use of miscible solvent systems where the active ingredient is dissolved in a first solvent and then precipitated out by introducing a second solvent that is miscible with the first solvent but immiscible with the solution, specifically using solvents like toluene and hexane or methanol and water, to produce uniformly sized particles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional particle production methods are used, then particles can be produced, but the particles exhibit non-uniform size distribution and poor solubility

Engineering Contradiction:
Improveparticle size uniformityVSAvoidsolubility consistency
Core Design Contradiction:
Manufacturing precisionVSReliability

Solution Approach 1:

The invention changes the solvent system parameters by selecting specific solvent combinations (first solvent in which the active ingredient is soluble, and second solvent miscible with the first but immiscible with the solution) to control the precipitation process. This parameter change enables uniform particle formation while maintaining consistent solubility characteristics.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention introduces a two-solvent system as an intermediary mechanism where the first solvent dissolves the active ingredient and the second solvent triggers controlled precipitation. This intermediary solvent system mediates between the active ingredient and the final particle formation, ensuring uniform size distribution and consistent solubility.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If particle size is reduced to improve release rate, then faster therapeutic agent release is achieved, but particle uniformity becomes harder to control

Engineering Contradiction:
Improverelease rateVSAvoidparticle size distribution
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The invention utilizes phase transition by introducing the second solvent that causes the active ingredient to precipitate from the solution. This controlled phase transition from dissolved state to solid particle state enables the formation of small, uniform particles with consistent size distribution, achieving both fast release rate and manufacturing precision.

Inventive Principle:
Principle #36Phase transitions

3Reliability

If existing solvent systems are used for particle production, then particles can be formed, but stability and pharmacokinetic properties are compromised

Engineering Contradiction:
Improvepharmacokinetic consistencyVSAvoidparticle stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The invention optimizes solvent system parameters by carefully selecting the first and second solvents based on their miscibility characteristics and the active ingredient's solubility. This parameter optimization ensures that the resulting particles have both improved stability and consistent pharmacokinetic properties.

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 produces particles with improved solubility, stability, and pharmacokinetics, resulting in smaller, more uniform particles suitable for medical formulations with enhanced properties compared to larger particles.

Implementation Method 1

mixing a second solvent with the first solution to produce an emulsified solution; the second solvent is miscible with the first solvent, but is immiscible with the first solution

Methodology Applied
Scientific EffectPrecipitation: Precipitation

Implementation Method 2

forming the particles of the active ingredient by mixing a second solvent with the first solution to produce an emulsified solution

Methodology Applied
Scientific EffectEmulsion: Emulsion

Implementation Method 3

takes advantages in the differences between solubilities of the therapeutic agent in two miscible solvent systems, so that the therapeutic agent soluble in one solvent system precipitates when another solvent is introduced therein

Methodology Applied
Scientific EffectSolubility difference: Solvation

Data Source

PatentEP3638212B1Methods for producing particles of an active ingredient
Publication Date: 2024.05.01 SAVIOR LIFETEC CORP
  • EP3638212B1 patent drawingFigure 1A~1B

AI summary

Disclosed herein are particles of an active ingredient, a composition comprising the same, and a method for producing the same. The method disclosed herein comprises the steps of, (a) forming a first solution by dissolving the active ingredient in a first solvent; (b) forming the particles of the active ingredient by mixing a second solvent with the first solution to produce an emulsified solution. Moreover, the second solvent is miscible with the first solvent, but is immiscible with the first solution.