Injectable Leuprolide Polymer Composition Impurity Reduction
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Solution Overview
Problem
Existing injectable biodegradable polymeric formulations for sustained release of nucleophilic bioactive substances suffer from significant impurity generation due to reactions between the bioactive substances and residual monomers of the polymer, leading to stability issues and regulatory compliance challenges.
Innovation Solution
The development of a stable, injectable biodegradable polymeric composition that reduces or prevents the formation of impurities by using lactate-based polymers with low residual lactide monomer content, low extractable oligomers, and low acid numbers, without the addition of acid additives.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If biodegradable polymeric formulations are used for sustained release of nucleophilic bioactive substances, then sustained release capability is improved, but impurity generation increases due to reactions between bioactive substances and residual monomers
Solution Approach 1:
The patent removes residual monomers and oligomers from the polymeric formulation through purification processes, extracting the harmful components that cause impurity generation while maintaining the sustained release functionality of the polymer matrix
Solution Approach 2:
The patent modifies the molecular weight distribution and composition parameters of the polymeric formulation to reduce the presence of reactive monomers and oligomers, thereby decreasing impurity generation while preserving sustained release capability
2Loss of time
If biodegradable polymeric formulations are used for sustained release, then administration frequency is reduced, but manufacturing complexity increases
Solution Approach 1:
The patent divides the manufacturing process into distinct modular steps including polymer synthesis, purification, formulation, and quality testing, making each stage more manageable and reproducible while maintaining the complexity necessary for sustained release functionality
Solution Approach 2:
The patent employs disposable single-use vials and pre-filled syringes for administration, simplifying the manufacturing and storage requirements while maintaining the sustained release capability over the product's shelf life
3Reliability
If biodegradable polymeric formulations are used for sustained release, then patient compliance is improved, but product stability deteriorates due to reactions between bioactive substances and polymer
Solution Approach 1:
The patent introduces stabilizing agents and protective intermediaries that prevent direct harmful interactions between the nucleophilic bioactive substance and the polymeric matrix, maintaining product stability while preserving sustained release functionality
Solution Approach 2:
The patent creates a chemically inert environment within the polymeric formulation by controlling the molecular structure and composition to prevent unwanted reactions between the bioactive substance and polymer, thereby maintaining stability during storage and administration
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 proposed solution achieves improved stability of the polymeric composition, significantly reducing the formation of bioactive substance-related impurities and preventing premature degradation of the biodegradable polymer, thus enhancing the quality and regulatory compliance of the drug product.
Implementation Method 1
The biodegradable polymer and bioactive substances are dissolved in a biocompatible organic solvent to provide a liquid or flowable composition. When the liquid composition is injected into the body, the solvent dissipates into the surrounding aqueous environment, and the polymer forms a solid or gel depot from which the bioactive substance is released over a long period of time.
Implementation Method 2
When the liquid composition is injected into the body, the solvent dissipates into the surrounding aqueous environment, and the polymer forms a solid or gel depot
Data Source
AI summary
A method and system for treating a hormonal disorder comprising injecting a composition comprising an effective amount of leuprolide or a salt thereof to a patient suffering from the hormonal disorder, with the system comprising N-methylpyrrolidone (NMP) and a polymer having a weight average molecular weight between 5,000 and 50,000 Dalton, an acid number of less than 3 mgKOH/g.