API Nanocrystallization in Aqueous Polymers to Limit Particle Growth
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Solution Overview
Problem
Existing methods for crystallizing active pharmaceutical ingredients (APIs) often result in particle size growth during crystallization, leading to reduced bioavailability due to inadequate dissolution rates, and amorphous APIs tend to crystallize during processing, storage, and administration, losing solubility advantages.
Innovation Solution
A method involving the contact of amorphous nanosized APIs with aqueous solutions containing polymers and/or copolymers, forming an admixture with a higher amorphous API content than the solubility limit, inhibiting particle size growth and achieving crystalline nanoparticles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If amorphous nanosized APIs are contacted with aqueous polymer solutions to induce crystallization, then the solubility advantage is lost, but particle size growth is inhibited and stable crystalline nanoparticles are obtained
Solution Approach 1:
The invention changes the physical state parameter of the API from amorphous to crystalline through controlled crystallization in aqueous polymer solutions, transforming the system from high solubility (amorphous) to high stability (crystalline) while maintaining nanoscale dimensions
Solution Approach 2:
Aqueous polymer solutions serve as an intermediary medium that enables controlled crystallization of amorphous nanosized APIs. The polymers facilitate the phase transition and stabilize the resulting crystalline nanoparticles, acting as a mediator between the amorphous starting material and the desired crystalline product
2Productivity
If API particle size is reduced through micronization/nanonization to increase dissolution rate, then bioavailability is improved, but particle size control becomes more difficult during subsequent processing
Solution Approach 1:
The invention performs preliminary crystallization in the aqueous polymer solution before final formulation processing. This preliminary action establishes controlled particle sizes and crystalline structures that are resistant to further aggregation during subsequent manufacturing steps, thereby maintaining particle size control throughout the process
Solution Approach 2:
The invention creates a composite system where crystalline API nanoparticles are stabilized within or by polymer matrices. This composite structure prevents particle aggregation and maintains size control, combining the dissolution benefits of small particles with the stability of a protected composite form
3Quantity of substance
If amorphous APIs are stabilized in polymeric matrices to maintain solubility, then solubility advantage is preserved, but significant amounts of polymer are required
Solution Approach 1:
Instead of using large amounts of polymer to stabilize amorphous APIs (conventional approach), the invention inverts the approach by using minimal polymer to facilitate crystallization. The resulting crystalline nanoparticles inherently provide stability without requiring high polymer loads for amorphous stabilization
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 maintains nanoparticle size and enhances bioavailability by preventing significant particle size increase, allowing for stable crystalline APIs with improved dissolution and permeability, reducing the need for high polymer content and avoiding mechanical stress.
Implementation Method 1
a method for crystallization of active pharmaceutical ingredient (API), the method comprising providing amorphous nanosized API, providing an aqueous solution comprising one or more polymers and/or copolymers, and contacting the amorphous nanosized API and the aqueous solution
Data Source
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Figure 3
Figure 4~5C
AI summary
The disclosure relates to methods for crystallization of active pharmaceutical ingredients (APIs), wherein the crystallization and crystal growth is controlled According to the method solid amorphous nanosized API and an aqueous solution comprising one or more polymers and/or copolymers are contacted so as to form a suspension comprising nanosized API in crystalline form.