Lyophilized Degarelix Composition for Reconstitution Viscosity Control
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Degarelix, a synthetic decapeptide used for prostate cancer treatment, forms gels in aqueous solution leading to depot formation and sustained release, which is not effectively controlled in existing manufacturing processes, affecting viscosity and bioavailability.
Innovation Solution
A method to control the viscosity of lyophilized degarelix by de-aggregating the peptide with acetic acid and lyophilizing it with specific conditions, ensuring a viscosity range of 2 to 12 mPas upon reconstitution, using mannitol and optionally a viscosity-reducing agent.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If degarelix is prepared using conventional synthesis methods, then the drug substance can be produced, but the viscosity and sustained release properties cannot be effectively controlled
Solution Approach 1:
The patent applies parameter changes by optimizing the acetic acid concentration (4.5-10.0% w/w) and water content (≤10% w/w) in the lyophilized degarelix drug substance to achieve controlled viscosity (2-12 mPas) upon reconstitution. This specific parameter range resolves the contradiction by providing precise viscosity control while maintaining manufacturability through established lyophilization processes.
Solution Approach 2:
The patent employs preliminary action by controlling the aggregation state of degarelix during the lyophilization process. The drug substance is prepared in advance with specific acetic acid and water content to ensure proper aggregation, which then controls the viscosity and sustained release properties upon reconstitution without requiring additional process steps.
2Duration of action of moving object
If degarelix forms gels in aqueous solution, then depot formation and sustained release are achieved, but viscosity control becomes difficult affecting bioavailability
Solution Approach 1:
The patent resolves this contradiction by changing the physical-chemical parameters of the lyophilized drug substance, specifically controlling acetic acid content (4.5-10.0% w/w) and water content (≤10% w/w). These parameter changes ensure that upon reconstitution, the degarelix forms gels with controlled viscosity (2-12 mPas), achieving both sustained release through depot formation and precise viscosity control for consistent bioavailability.
3Reliability
If the viscosity of reconstituted drug product is not controlled, then manufacturing is simpler, but depot formation and sustained release properties are inconsistent
Solution Approach 1:
The patent applies preliminary action by incorporating viscosity control measures during the lyophilization process itself. The drug substance is prepared with controlled acetic acid and water content before lyophilization, ensuring that the resulting product will have consistent viscosity (2-12 mPas) upon reconstitution. This eliminates the need for additional viscosity adjustment steps while ensuring reliable product quality.
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 method achieves controlled depot formation and sustained release of degarelix, enhancing bioavailability and ensuring consistent product quality.
Implementation Method 1
A method to control the viscosity of lyophilized degarelix by de-aggregating the peptide with acetic acid
Implementation Method 2
lyophilizing it with specific conditions
Implementation Method 3
using mannitol and optionally a viscosity-reducing agent
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention provides methods for producing a lyophilized degarelix product which, upon reconstitution with water for injection in an amount of 20 mg/ml, shows a viscosity of up to 15 mPas. The present invention also provides a lyophilized degarelix drug substance which shows, upon dissolution in water in an amount of 20 mg/ml, a viscosity of up to 3.2 mPas, and processes for providing this lyophilized degarelix drug substance.