Amorphous PKI Nanoparticle Compositions for Oral Solubility Stability
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Solution Overview
Problem
Existing formulations of protein kinase inhibitors (PKIs) face challenges with poor aqueous solubility and stability, leading to limited bioavailability and efficacy, particularly at neutral pH in the gastrointestinal tract, necessitating improved dissolution characteristics for oral delivery.
Innovation Solution
The development of stable, amorphous hybrid nanoparticles comprising PKIs and polymeric stabilizing and matrix-forming components, optionally with solubilizers, formed through continuous precipitation methods, enhancing solubility and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If protein kinase inhibitors are formulated for oral delivery, then bioavailability can be improved, but poor aqueous solubility and stability at neutral pH limit dissolution characteristics
Solution Approach 1:
The patent transforms the crystalline PKI into an amorphous form, changing the physical state parameter to improve dissolution characteristics. The amorphous form lacks the ordered crystal lattice, increasing molecular mobility and solubility while maintaining stability through encapsulation in a polymer matrix.
Solution Approach 2:
The patent creates a composite material system combining the amorphous PKI with a stabilizing polymer matrix. This composite structure provides both solubility enhancement from the amorphous state and stability from the polymer encapsulation, resolving the contradiction between solubility and stability.
2Productivity
If amorphous form is used to enhance solubility, then dissolution rate improves, but stability may be compromised without proper stabilization
Solution Approach 1:
The stabilizing polymer acts as an intermediary between the amorphous PKI and the aqueous environment. It encapsulates the amorphous drug, maintaining its high-energy state and solubility advantage while protecting it from degradation, thus enabling both fast dissolution and stability.
Solution Approach 2:
The patent applies different properties to different parts of the formulation: the PKI is in an amorphous state for high dissolution rate, while the polymer matrix provides a stable protective environment. This local differentiation of physical states optimizes both dissolution and stability.
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 amorphous hybrid nanoparticles demonstrate enhanced solubility and stability, improving bioavailability and efficacy of PKIs by maintaining solubility in intestinal fluids, as evidenced by increased plasma levels and dissolution rates.
Implementation Method 1
stable, amorphous hybrid nanoparticles of protein kinase inhibitors and polymeric stabilizing and matrix-forming components
Implementation Method 2
polymeric stabilizing and matrix-forming components
Data Source
AI summary
The present invention relates to the field of methods for providing pharmaceutical compositions comprising poorly water-soluble drugs. In particular the present invention relates to compositions comprising stable, amorphous hybrid nanoparticles, comprising at least one protein kinase inhibitor and at least one polymeric stabilizing and matrix-forming component, useful in pharmaceutical compositions and in therapy.