Amorphous Solid Dispersion via Dual Hydrolysis PVA Matrix
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Hydrophilic polymers like polyvinyl alcohol (PVA) with high polarity struggle to form amorphous solid dispersions with poorly soluble active pharmaceutical ingredients (APIs), leading to undesirable two-phase systems and reduced bioavailability, as they tend to swell and dissolve quickly, requiring additional processing steps for sustained release.
Innovation Solution
Combining PVAs with different degrees of hydrolysis, where the first PVA has a higher degree of hydrolysis than the second, creates a polymer matrix that facilitates the formation of a stable amorphous solid dispersion of APIs, improving stability and sustained release properties by varying hydrophilic/lipophilic properties to match API solubility and release requirements.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If hydrophilic polymers with high polarity (99% or 98% hydrolyzed PVAs) are used to form amorphous solid dispersions, then the polymer matrix shows high solubility and fast release rates, but the API stability deteriorates due to undesirable two-phase system formation and recrystallization
Solution Approach 1:
The patent combines two different PVA types (hydrophilic PVA and amphiphilic PVA) into a composite polymer matrix. The hydrophilic PVA (99% or 98% hydrolyzed) provides fast release capability, while the amphiphilic PVA (90-96% hydrolyzed) provides API stability by preventing two-phase system formation. This composite approach allows both fast release and API stability to coexist.
Solution Approach 2:
The patent applies different polymer properties to different functional requirements: the hydrophilic PVA component addresses the release rate requirement, while the amphiphilic PVA component addresses the API stability requirement. Each polymer type contributes its specific local quality (hydrophilicity or amphiphilicity) to solve different aspects of the problem.
2Productivity
If highly hydrolyzed PVAs (99% or 98%) are used as polymer matrix, then fast release rates are achieved, but additional processing steps are required to achieve sustained release profiles
Solution Approach 1:
By incorporating amphiphilic PVA (90-96% hydrolyzed) into the polymer matrix alongside hydrophilic PVA, the system inherently provides sustained release capability without requiring additional processing steps such as sustained release coatings. The amphiphilic component modulates the release profile through its balanced hydrophilic-lipophilic properties.
Solution Approach 2:
The patent changes the polymer composition parameters by selecting PVAs with specific hydrolysis degrees (99% or 98% combined with 90-96%). This parameter change in polymer selection directly achieves sustained release profiles without needing additional processing steps, as the polymer composition itself controls the release kinetics.
3Quantity of substance
If hydrophilic polymers are used to stabilize APIs, then high polarity provides good solubility, but amorphous dispersion formation becomes difficult leading to phase separation
Solution Approach 1:
The patent creates a composite polymer matrix combining hydrophilic PVA (for solubility) with amphiphilic PVA (for dispersion stability). The amphiphilic component, with its balanced hydrophilic-lipophilic properties, specifically addresses the amorphous dispersion stability issue by preventing phase separation, while the hydrophilic component maintains high solubility.
Solution Approach 2:
The amphiphilic PVA acts as an intermediary between the hydrophilic PVA and the lipophilic API. Its dual nature (containing both hydrophilic and lipophilic character) allows it to mediate the interaction, facilitating amorphous dispersion formation and preventing phase separation by bridging the polarity gap between the hydrophilic polymer and lipophilic API.
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 approach enhances bioavailability by preventing phase separation and prolonging release profiles, allowing for tailored release characteristics and improved stability of poorly soluble APIs, reducing the need for additional processing steps.
Implementation Method 1
mixing the first polyvinyl alcohol, the second polyvinyl alcohol and optionally further pharmaceutically acceptable components and the active pharmaceutical ingredient at a temperature above the glass transition temperature or melting temperature of the polymer matrix
Implementation Method 2
mixing the first polyvinyl alcohol, the second polyvinyl alcohol and optionally further pharmaceutically acceptable components and the active pharmaceutical ingredient at a temperature above the glass transition temperature or melting temperature of the polymer matrix
Data Source
AI summary
The present invention relates to a method for producing an amorphous solid dispersion of at least one active pharmaceutical ingredient in a polymer matrix. The Invention further relates to a pharmaceutical composition using polymers as an excipient and particularly to an improved pharmaceutical composition comprising polyvinyl alcohol grades with different degrees of hydrolysis, which is suitable to stabilize active pharmaceutical ingredients.