Ionized Polymer Salts for High-Loading ASD Drug Release
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Solution Overview
Problem
Existing amorphous solid dispersion (ASD) formulations face challenges with drug release at higher drug loadings, leading to incomplete release and increased pill burden, especially with enteric polymers like HPMCAS and HPMCP, which exhibit slow drug release even at low loadings and decline dramatically at elevated loads.
Innovation Solution
The use of polymer salts, specifically enteric polymer salts with ionized carboxylic groups and counterions, to enhance drug release in ASDs, making them more robust to buffer capacity variations and improving drug loading without compromising release performance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If higher drug loading is used in ASD formulations, then pill burden is reduced, but drug release becomes incomplete and release performance declines dramatically
Solution Approach 1:
The invention changes the ionization state parameter of the polymer from protonated (acidic) form to salt form (ionized) by reacting with bases such as sodium hydroxide, potassium hydroxide, or ammonium hydroxide. This parameter change transforms the polymer's dissolution behavior to maintain robust drug release across varying buffer capacities, enabling higher drug loadings (up to 80-90 wt%) while preserving complete drug release performance.
2Quantity of substance
If enteric polymers like HPMCAS and HPMCP are used in ASD formulations, then solubility enhancement is achieved, but drug release becomes slow even at low loadings and declines at elevated loads
Solution Approach 1:
The invention changes the ionization parameter of enteric polymers from protonated to ionized salt form, which fundamentally alters the dissolution mechanism. The salt forms exhibit pH-independent dissolution behavior with robust release rates, eliminating the slow and loading-dependent release characteristic of protonated enteric polymers while maintaining solubility enhancement capabilities.
3Device complexity
If protonated polymers are used, then formulation simplicity is maintained, but drug release becomes highly sensitive to buffer capacity variations
Solution Approach 1:
The invention changes the polymer's chemical state from protonated to ionized salt form, which fundamentally improves adaptability to buffer capacity variations. The salt forms exhibit pH-independent dissolution behavior, making drug release robust across different gastrointestinal conditions while maintaining formulation simplicity through straightforward salt formation processes using common bases.
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 polymer salts maintain similar drug release rates across varying buffer capacities, enabling higher drug loadings with improved release performance compared to protonated polymers, addressing the issues of slow release and incomplete drug delivery.
Implementation Method 1
polymer salts, specifically enteric polymer salts with ionized carboxylic groups and counterions
Implementation Method 2
polymer salts with ionized carboxylic groups and counterions
Data Source
AI summary
The invention generally relates to polymer salts for improved drug delivery from amorphous solid dispersions. In certain aspects, the invention provides an amorphous solid dispersion (ASD) composition comprising an active pharmaceutical agent (API); and a polymer salt that enables dispersion of the API in an amorphous matrix.