Lyophilized Copanlisib Salt Formulation Using Lactose or Trehalose
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Solution Overview
Problem
Existing pharmaceutical formulations using mannitol as a bulking agent face stability issues, risk of vial breaking, and destabilization due to water release, especially at higher pH levels, which affects the stability and solubility of copanlisib, a water-sensitive drug.
Innovation Solution
A lyophilized pharmaceutical formulation comprising copanlisib salt with lactose or trehalose as bulking agents, optionally with glycine, which improves stability and solubility by modifying the glass transition temperature and avoiding the risks associated with mannitol, and is processed to maintain stability and purity for at least 72 hours.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If mannitol is used as a bulking agent, then the formulation can provide bulk and structure, but it causes vial breaking risk and water release that destabilizes the drug
Solution Approach 1:
The patent removes mannitol from the formulation and replaces it with trehalose or lactose as the bulking agent. This extraction of the problematic substance eliminates the source of vial breaking and water release issues while maintaining the necessary bulk and structural properties of the lyophilized formulation.
Solution Approach 2:
Trehalose or lactose serves as an intermediary substance that performs the same functional role as mannitol (providing bulk and structure) but without the harmful side effects. These alternative bulking agents do not cause vial breaking or release water that would destabilize the water-sensitive copanlisib drug.
2Quantity of substance
If pH is increased above 5.5, then solubility may improve, but copanlisib precipitation occurs reducing stability
Solution Approach 1:
The patent optimizes the pH parameter to a specific range (above 5.5) where copanlisib maintains both solubility and stability. By carefully controlling this critical parameter and using appropriate buffering systems, the formulation achieves the desired balance between solubility and prevention of precipitation.
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 with lactose or trehalose provides enhanced stability and solubility at pH levels above 5.5, preventing precipitation and maintaining clarity and purity, thus improving the industrial production of injectable dosage forms.
Implementation Method 1
Glycine as Tg'-modifer (glass transition temperature modifier) capable of modifying a sufficiently Tg' of the pharmaceutical solution to higher temperatures
Implementation Method 2
The formulation of presented invention shows good stability and solubility at pH higher than 5.5
Data Source
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AI summary
The presented invention relates to a lyophilized pharmaceutical formulation comprising copanlisib salt and a bulking agent selected from lactose or trehalose and to a process for preparation thereof.