Anti-cancer Peptide Formulation Stability via Mannitol and Sucrose
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Solution Overview
Problem
Pharmaceutical formulations containing proteins and peptides are prone to degradation due to denaturation and aggregation, leading to instability and loss of bioactivity over time, especially during storage.
Innovation Solution
Development of stable liquid and lyophilized formulations of anti-cancer peptides with specific compositions, including 1-75 mg/ml of anti-cancer peptides, 5-30 mM acetate buffer, 10-80 mg/ml mannitol, and 0-30% sucrose, with a pH of 4.0-6.0, which include an HDM-2 binding component and a membrane resident component, to prevent particle formation and maintain stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If pharmaceutical formulations contain proteins and peptides, then therapeutic efficacy is achieved, but degradation and aggregation occur during storage
Solution Approach 1:
The patent applies parameter changes by optimizing pH (4.0-6.0 range), peptide concentration (1-75 mg/ml), and excipient concentrations to achieve stable formulations. The acetate buffer system at controlled pH and the specific combination of mannitol and sucrose create optimal conditions that prevent peptide degradation and aggregation during long-term storage.
Solution Approach 2:
The patent uses mannitol and sucrose as intermediary substances that protect the peptide from degradation. These excipients act as mediators by forming a protective matrix around the peptide molecules, preventing direct interactions that lead to aggregation and denaturation during storage.
2Duration of action of stationary object
If formulations are stored long-term, then therapeutic availability is maintained, but particle formation increases
Solution Approach 1:
The patent applies beforehand cushioning by incorporating mannitol and sucrose into the formulation before storage. These excipients create a protective environment that cushions the peptide molecules against stressors during long-term storage, preventing aggregation and particle formation even after years of storage.
Solution Approach 2:
The patent uses a composite formulation system combining peptide, acetate buffer, mannitol, and sucrose. This composite material approach creates a synergistic system where each component contributes to overall stability, with the excipients working together to prevent particle formation during extended storage periods.
3Quantity of substance
If formulations are concentrated, then dosing efficiency is improved, but aggregation increases
Solution Approach 1:
The patent uses mannitol and sucrose as intermediary substances that enable high peptide concentrations without aggregation. These excipients act as spacers and protective agents around peptide molecules, allowing the formulation to maintain high concentrations (1-75 mg/ml) while preventing the peptide-peptide interactions that would otherwise lead to aggregation.
Data Source
AI summary
Stable, liquid formulations of anti-cancer peptides where the formulation contains about 1-75 mg/ml of anti-cancer peptides, about 5-30 mM acetate buffer, about 10-80 mg/ml mannitol, and about 0-30% sucrose, where the formulation has a pH of about 4.0-6.0, and wherein the anti-cancer peptides include an HDM-2 binding component and a membrane resident component.