Siponimod Parenteral Formulation Stability
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Solution Overview
Problem
There is a need for stable parenteral formulations of siponimod that are suitable for long-term clinical studies and administrations, as existing lyophilized formulations have limited stability and shelf life.
Innovation Solution
A parenteral formulation comprising siponimod, cyclodextrin, a buffer agent, a solvent, and optionally a tonicity agent, which can be in liquid form and is suitable for intravenous administration, providing improved stability and shelf life.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If a lyophilized formulation of siponimod is used, then the formulation can be stored at freezing conditions, but the shelf life is limited to about 12 months which is not sufficient for long-term clinical studies
Solution Approach 1:
The patent changes the physical state parameter from lyophilized (solid) to liquid formulation, and modifies the storage temperature parameter from freezing conditions to refrigerated conditions (2-8°C). This parameter change enables the formulation to achieve extended shelf life of at least 15 months while maintaining stability, resolving the contradiction between stability and shelf life duration
Solution Approach 2:
The patent uses a composite formulation system comprising cyclodextrin inclusion complexes with siponimod, combined with specific buffer agents and stabilizers. This composite material approach enhances the stability of siponimod in liquid form and extends the shelf life to at least 15 months under refrigerated storage, overcoming the limitations of simple lyophilized formulations
2Quantity of substance
If a liquid parenteral formulation is prepared with high concentration of siponimod, then the dosage efficiency is improved, but the stability and shelf life are reduced
Solution Approach 1:
The patent employs cyclodextrin as an intermediary substance that forms inclusion complexes with siponimod. This mediator allows high concentrations of the hydrophobic active ingredient to be solubilized in aqueous medium while maintaining molecular stability. The cyclodextrin inclusion complex prevents precipitation and degradation, enabling both high concentration and enhanced stability in the liquid formulation
Solution Approach 2:
The patent employs stabilizers and buffer agents that provide short-term protection during storage, allowing the formulation to maintain stability at high concentrations. These auxiliary substances act as temporary protective measures that extend the effective shelf life without requiring freezing conditions, enabling concentrated liquid formulation to remain stable for at least 15 months under refrigerated storage
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 formulation achieves enhanced stability and shelf life of at least 15 months when stored at 2-8°C, making it suitable for long-term clinical studies and administrations.
Implementation Method 1
A parenteral formulation comprising (A) siponimod, (B) cyclodextrin
Implementation Method 2
a buffer agent
Data Source
AI summary
The present invention relates to a pharmaceutical formulation of siponimod which can be administered parenterally. In particular, the present invention relates to a parenteral solution comprising siponimod and a method for preparing said solution.