Fusidic Acid Crystalline Form Stability
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Solution Overview
Problem
Current solid forms of fusidic acid, such as the marketed hemihydrate, have stability and bioavailability issues due to polymorphism, affecting solubility, dissolution rate, and hygroscopicity, which impact its effectiveness in treating infectious diseases.
Innovation Solution
A novel crystalline form of fusidic acid is developed, characterized by specific Fourier Transform (FT)-NIR, FTIR-ATR, and X-ray powder diffraction spectra, offering improved stability and bioavailability through a controlled crystallization process involving solvents like acetonitrile and ethanol, resulting in a thermodynamically more stable anhydrous form.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the marketed hemihydrate form of fusidic acid is used, then it is available for clinical application, but it exhibits stability issues and bioavailability problems due to polymorphism
Solution Approach 1:
The patent applies parameter changes by transforming fusidic acid from the hemihydrate solid form to an anhydrous crystalline form through controlled crystallization processes. This changes the physical and chemical parameters of the drug substance, resulting in improved stability while maintaining or enhancing bioavailability through optimized dissolution properties.
Solution Approach 2:
The invention utilizes phase transitions by converting fusidic acid from a hydrated crystalline phase (hemihydrate) to an anhydrous crystalline phase. This phase transition eliminates the instability associated with the hemihydrate form while producing a more stable anhydrous form with improved pharmaceutical properties.
2Productivity
If different crystal forms of fusidic acid are used, then solubility and dissolution rate can be optimized, but polymorphism causes variability in hygroscopicity and stability
Solution Approach 1:
The patent employs parameter changes by systematically varying crystallization conditions (solvent type, temperature, concentration) to produce a specific anhydrous crystalline form of fusidic acid. This controlled parameter change results in a crystal form with optimized dissolution rate and reduced hygroscopicity compared to other polymorphic forms.
Solution Approach 2:
The invention converts the potential harm of polymorphism (which causes variability in hygroscopicity and stability) into a benefit by deliberately selecting and controlling the crystallization process to produce a specific anhydrous crystal form. This form eliminates the adverse effects of unwanted polymorphism while retaining the advantages of optimized dissolution and stability.
3Reliability
If the anhydrous crystalline form is produced through controlled crystallization, then stability and bioavailability are improved, but the process requires specific solvents and conditions
Solution Approach 1:
The patent utilizes phase transitions as the core mechanism for producing the anhydrous crystalline form. By controlling the phase transition from dissolved state to crystalline precipitate through systematic variation of crystallization parameters, the process achieves improved stability and bioavailability while maintaining operational simplicity.
Solution Approach 2:
The invention applies parameter changes in a controlled and systematic manner during crystallization. By adjusting parameters such as solvent composition, temperature, and concentration in a stepwise fashion, the process achieves the desired anhydrous crystal form without requiring overly complex equipment or procedures.
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 novel crystalline form exhibits enhanced stability and bioavailability, maintaining effectiveness in treating infectious diseases by optimizing solubility and dissolution rates, and can be converted back to the marketed hemihydrate form for specific applications.
Implementation Method 1
a novel crystalline form of fusidic acid and a process for the preparation of said crystalline fusidic acid
Data Source
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AI summary
The present invention relates to processes for the crystallisation and for the preparation and isolation of a novel crystalline form of fusidic acid, to the use of said processes in the manufacture of pharmaceutical formulation or medicament, and to the use of said crystalline fusidic acid form for the treatment of bacterial infections.