Pyripyropene Suspension Stability via Crystalline Form Conversion
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Solution Overview
Problem
The formulation of pyripyropene derivative I as an aqueous suspension concentrate faces stability issues due to particle growth and agglomeration, particularly at high purities, leading to gelling problems, which existing surfactant combinations struggle to address effectively.
Innovation Solution
A method involving the preparation of an aqueous slurry with coarse particles of pyripyropene derivative I in its crystalline form B, followed by comminution to achieve fine particles in form Y, using a surfactant system that stabilizes the formulation without requiring specific surfactant combinations, thereby enhancing stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional surfactant combinations are used to formulate pyripyropene derivative I as an aqueous suspension concentrate, then the formulation can be prepared, but stability problems occur due to particle growth and agglomeration
Solution Approach 1:
The patent changes the crystal form parameter of the active ingredient from conventional forms to a specific metastable crystalline form, which fundamentally alters the formulation's stability characteristics. This parameter change enables stable suspension concentrates without requiring complex surfactant combinations, directly resolving the contradiction between formulability and stability.
Solution Approach 2:
The patent performs preliminary conversion of the active ingredient to the specific crystalline form before formulation. This preliminary action prevents subsequent particle growth and agglomeration during storage, addressing the stability issue before it occurs rather than attempting to mitigate it after formulation.
2Reliability
If high purity pyripyropene derivative I is used in the formulation, then pesticidal efficacy is improved, but gelling problems occur making formulation difficult
Solution Approach 1:
The patent changes the crystal form parameter of high purity pyripyropene derivative I, which eliminates the gelling problem while maintaining high purity. This allows high purity material to be formulated easily without processing difficulties, resolving the contradiction between efficacy and manufacturability.
3Stability of the object's composition
If complex surfactant combinations are used to stabilize the suspension, then particle growth is reduced, but formulation complexity and cost increase
Solution Approach 1:
The patent changes the crystal form parameter to achieve inherent stability, which eliminates the need for complex surfactant combinations. This simple parameter change reduces formulation complexity while maintaining stability, directly resolving the contradiction between stability and simplicity.
Solution Approach 2:
The patent extracts the stability requirement from the surfactant system and embeds it in the crystal structure itself. By taking out the need for complex stabilizing agents and incorporating stability into the fundamental crystal form, the formulation becomes simpler while maintaining stability.
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 significant stability of the aqueous suspension concentrate by converting a substantial portion of pyripyropene derivative I into form Y, preventing particle growth and agglomeration, even at high purities, resulting in a stable formulation with improved storage stability.
Implementation Method 1
providing an aqueous slurry of coarse particles of the pyripyropene derivative I, wherein the pyripyropene derivative I is at least partially present in its crystalline form B... comminuting the coarse particles in the slurry of the compound of formula I, which is at least partially present in its form B... converting a substantial portion of pyripyropene derivative I into form Y
Implementation Method 2
aqueous suspension concentrates are liquid aqueous formulations, which contain the active ingredient in the form of a suspension of particles suspended in the aqueous phase of the formulation containing a suitable surfactant for stabilizing the solid particles
Data Source
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AI summary
The present invention relates to a method for producing an aqueous suspension concentrate formulation and novel suspension concentrate formulations of the compound of formula I. The method comprises: a) providing an aqueous slurry of coarse particles of the compound of the formula I, where the compound of the formula I is at least partially present in its crystalline form B, which, in an X-ray powder diffractogram at 25°C and Cu-Kalpha radiation, shows at least three, preferably at least four, in particular at least 5 or at least 7 or at least 9 or all of the following reflexes, given as 2theta values:8.0± 0.2°, 9.5± 0.2°, 10.7± 0.2°, 11.0± 0.2°, 11.2± 0.2°,11.7± 0.2°, 14.2± 0.2°, 15.6± 0.2°, 6.5± 0.2°, 17.7± 0.2°, 21.5± 0.2°; b) comminuting the coarse particles in the slurry of the compound of formula I, which is at least partially present in its form B, in the presence of the at least one surfactant.