Oxadiazole Solid Formulation Using Citric Acid for Physical Stability
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Solution Overview
Problem
Existing 1,2,4-oxadiazole derivatives are inconvenient for widespread medical use due to their physical forms as oils or deliquescent solids, which complicate handling, mixing, quality control, and storage, and are not suitable for industrial drug manufacturing processes.
Innovation Solution
A solid formulation is achieved by mixing 1,2,4-oxadiazole derivatives with citric acid and/or saccharin, forming stable salts that maintain physical stability over time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If 1,2,4-oxadiazole derivatives are used in their native form, then they maintain their chemical structure and activity, but they exist as oils or deliquescent solids that are inconvenient for handling, mixing, quality control, and storage
Solution Approach 1:
The patent applies parameter changes by converting the physical state of the 1,2,4-oxadiazole derivative from oil or deliquescent solid to stable solid form through salt formation with citric acid and/or saccharin. This chemical modification changes the physical parameters (state, stability) while maintaining the active ingredient's identity and activity.
Solution Approach 2:
The patent creates a composite material system by combining the 1,2,4-oxadiazole derivative with citric acid and/or saccharin to form a stable solid formulation. The composite consists of the active ingredient plus stabilizing agents that prevent deliquescence and improve handling properties.
2Stability of the object's composition
If conventional acids are used to form addition salts with 1,2,4-oxadiazole derivatives, then salt formation occurs, but the resulting products are sticky oils or hygroscopic solids that achieve quick deliquescence
Solution Approach 1:
The patent uses citric acid and saccharin as sacrificial stabilizing agents that form stable solid complexes with the 1,2,4-oxadiazole derivative. These agents prevent deliquescence through specific molecular interactions, transforming an inherently unstable compound into a stable solid formulation suitable for pharmaceutical use.
Solution Approach 2:
The patent changes the chemical parameters by selecting specific acids (citric acid and/or saccharin) with particular properties (pKa, molecular structure) that enable stable solid salt formation. The molar ratio parameter is also optimized (at least 2:1 acid to derivative) to ensure complete stabilization and prevent deliquescence.
Data Source
AI summary
A solid formulation including at least one 1,2,4-oxadiazole derivative of formula (I):wherein R1, R2, R3, R4 and R5 are each independently selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy and C1-C3 thioalkyl; and citric acid and/or saccharin, wherein the molar ratio in the solid formulation between the total amount of citric acid and/or saccharin and the amount of the 1,2,4-oxadiazole derivative(s) ranges from about 2 to about 20. Also a process for manufacturing the solid composition and a method for increasing the physical stability of a 1,2,4-oxadiazole derivative of formula (I).