Polyether-Polyester Copolymer Stability via Acidic Protonation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current pharmaceutical compositions for sustained release of active pharmaceutical ingredients face challenges in maintaining stability, particularly in aqueous environments, where degradation issues arise due to nucleophilic-induced polyester degradation.
Innovation Solution
A pharmaceutical composition comprising a polyether-polyester copolymer, a nucleophilic compound, an organic solvent, and up to 10% of an acidic compound with a pKa of less than 3, which prevents degradation without prior salt formation, forming a semi-solid depot upon injection into an aqueous environment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If a nucleophilic compound is used as an active pharmaceutical ingredient in a polyether-polyester copolymer formulation, then the drug can be delivered via sustained release, but the polyester copolymer degrades over time due to nucleophilic attack
Solution Approach 1:
An acidic compound with pKa less than 3 is introduced as an intermediary substance that mediates between the nucleophilic API and the polyester copolymer. The acid protonates the nucleophilic groups, preventing direct nucleophilic attack on the ester bonds while allowing sustained release functionality to be maintained.
Solution Approach 2:
The pH environment within the formulation is modified by adding the acidic compound, changing the protonation state of the nucleophilic API. This parameter change (lowering pH) reduces the nucleophilicity of the API, thereby preventing polymer degradation while maintaining drug delivery capabilities.
2Stability of the object's composition
If prior salt formation between the acidic compound and nucleophilic compound is performed to prevent degradation, then polymer stability improves, but the formulation process becomes more complex
Solution Approach 1:
Instead of performing salt formation as a preliminary step before mixing, the acidic compound is included in the final formulation to act in situ. This eliminates the need for separate salt formation steps while achieving the same protective effect against nucleophilic degradation.
Solution Approach 2:
The acidic compound within the formulation self-regulates the nucleophilicity of the API through protonation, providing continuous protection against degradation without requiring external intervention or complex processing steps. The formulation protects itself through the inherent properties of the included acid.
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 composition exhibits improved stability with reduced degradation of the polyether-polyester copolymer, maintaining the active pharmaceutical ingredient's efficacy and stability for extended periods, even after storage, by preventing nucleophilic-induced degradation and forming a stable depot.
Implementation Method 1
the presence of a specific amount of an acid with a specific low pKa prevents nucleophile induced polyester degradation
Implementation Method 2
forming a semi-solid depot upon injection into an aqueous environment
Implementation Method 3
forming a semi-solid depot upon injection into an aqueous environment
Data Source
AI summary
The present invention provides a pharmaceutical composition comprising or consisting of at least one polyether-polyester copolymer, wherein the copolymer has the formula: B(A)n wherein B represents a polyether and comprises polyethylene glycol (PEG), each A represents a polyester arm and n is an integer from 1 to 8; at least one nucleophilic compound; at least one organic solvent; and up to 10% (w/w) of at least one acidic compound having a pKa(H2O) of less than 3.