PVA Amorphous Solid Dispersion for API Solubility
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Solution Overview
Problem
Poorly soluble active pharmaceutical ingredients (APIs) face reduced bioavailability due to instability and recrystallization in amorphous solid dispersions, particularly when pH changes from acidic gastric to neutral intestinal environments, limiting the effectiveness of existing pharmaceutical compositions.
Innovation Solution
A pharmaceutical composition using polyvinyl alcohol (PVA) with a hydrolysis degree of 72% to 85% and viscosity of 2 mPas to 4 mPas, which forms an amorphous solid dispersion with APIs, enhancing supersaturation properties and maintaining stability across pH shifts, particularly for weakly basic APIs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If amorphous solid dispersions are used to improve solubility of poorly soluble APIs, then solubility is enhanced, but stability deteriorates due to recrystallization and precipitation
Solution Approach 1:
The patent applies parameter changes by precisely controlling the hydrolysis degree of PVA within 72-85% and viscosity within 2-4 mPas. This specific parameter range optimizes the polymer's ability to maintain supersaturation while preventing recrystallization, resolving the contradiction between solubility enhancement and stability
Solution Approach 2:
PVA acts as an intermediary substance between the API and the aqueous environment. The polymer matrix mediates the dissolution process, maintaining supersaturation and preventing direct crystallization of the API, thus stabilizing the amorphous dispersion while enhancing solubility
2Quantity of substance
If PVA with high hydrolysis degree is used to enhance solubility, then supersaturation is improved, but stability after pH change deteriorates
Solution Approach 1:
The patent identifies and applies specific parameter ranges for PVA (hydrolysis degree 72-85%, viscosity 2-4 mPas) that optimize performance across pH changes. This precise parameter control ensures the polymer maintains supersaturation in acidic media while remaining stable in neutral intestinal environments
3Ease of manufacture
If conventional PVA grades are used in amorphous solid dispersions, then manufacturing is simplified, but bioavailability deteriorates due to rapid recrystallization
Solution Approach 1:
The patent specifies precise parameter ranges for PVA (hydrolysis degree 72-85%, viscosity 2-4 mPas) that can be manufactured using conventional processes while dramatically improving bioavailability. The parameters are set to prevent recrystallization during dissolution, ensuring reliable drug absorption in the intestine
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 PVA composition significantly improves the bioavailability of poorly soluble APIs by maintaining supersaturation and preventing crystallization, even in neutral media, leading to enhanced solubility and prolonged release of APIs.
Implementation Method 1
The formulation of amorphous solid dispersions is a well-known strategy to improve the bioavailability of poorly water-soluble drug substances
Implementation Method 2
The PVA composition significantly improves the bioavailability of poorly soluble APIs by maintaining supersaturation and preventing crystallization
Data Source
AI summary
The present invention relates to pharmaceutical compositions using polymers as an excipient. Particularly, the invention relates to a pharmaceutical composition comprising polyvinyl alcohol which is suitable to enhance solubility of poorly soluble active pharmaceutical ingredients in aqueous media. The present invention also relates to a method for enhancing solubility of poorly soluble active pharmaceutical ingredients.