Botulinum Toxin Prefilled Glass Container for Aqueous Stability
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Solution Overview
Problem
Existing botulinum toxin formulations are unstable, particularly at alkaline pH and heat-labile, leading to rapid loss of activity upon dilution, and current lyophilized products require reconstitution, which is inconvenient and prone to sterility issues, with limited shelf life and increased risk of contamination.
Innovation Solution
A prefilled glass container, such as a syringe, vial, or ampoule, containing an aqueous botulinum toxin formulation that maintains stability with minimal activity loss (less than 25%) for up to 24 months at various temperatures, ensuring high pH stability and low subvisible particle counts, making it suitable for prolonged storage and use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If botulinum toxin is formulated as a dilute aqueous solution for injection, then it is ready for immediate use without reconstitution, but the toxin rapidly loses activity due to instability in aqueous solution
Solution Approach 1:
The patent changes the pH parameter of the aqueous formulation to a slightly acidic range (pH 5.5-7.0), which stabilizes the botulinum toxin while maintaining solubility and activity. This parameter optimization allows the toxin to remain stable in aqueous solution without requiring lyophilization, thus resolving the contradiction between convenience and stability.
2Reliability
If botulinum toxin is formulated as a lyophilized product, then stability is improved, but reconstitution is required which is inconvenient and prone to sterility issues
Solution Approach 1:
The patent performs preliminary stabilization by formulating the botulinum toxin in a pre-stabilized aqueous solution with optimized pH and stabilizing agents before filling into the syringe. This preliminary action eliminates the need for reconstitution at the point of use, providing both stability and convenience simultaneously.
3Duration of action of stationary object
If botulinum toxin is stored at ambient temperature, then shelf life and storage flexibility are extended, but toxin activity deteriorates faster
Solution Approach 1:
The patent introduces stabilizing agents (such as amino acids, proteins, or surfactants) as intermediaries that protect the botulinum toxin from degradation. These stabilizers form protective complexes with the toxin, enabling it to maintain activity at ambient temperatures for extended periods, thus resolving the contradiction between storage flexibility and activity retention.
Data Source
AI summary
The present invention relates to a prefilled glass container, such as a prefilled glass syringe, comprising an aqueous botulinum toxin formulation. The aqueous botulinum toxin formulation in the prefilled container is stable at low to ambient temperature for a prolonged time period. Furthermore, the present invention relates to a kit comprising the botulinum toxin prefilled container, and to the use of the botulinum toxin prefilled container in therapeutic and cosmetic applications.