Spray Drying 21-Disodium Phosphate Pregnaned Derivatives
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Solution Overview
Problem
Existing methods for preparing 21-disodium phosphate pregnane derivatives often result in significant degradation and contamination, making it difficult to obtain high-purity solid forms suitable for pharmaceutical applications, particularly when drying these compounds.
Innovation Solution
A spray drying process is employed to minimize degradation, using a solution concentration of 2-30% w/w, preferably 3-5% w/w in water, at temperatures between 65°C to 105°C, and pH 7.6-9, to produce amorphous solid 21-disodium phosphate compounds with low levels of degradation products and solvates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional drying methods (evaporation under reduced pressure or freeze drying) are used to obtain solid 21-disodium phosphate compounds, then the compounds can be isolated, but significant degradation occurs during drying resulting in low purity products
Solution Approach 1:
The patent changes the drying parameters by using spray drying at controlled temperatures (65-105°C) with rapid atomization, compared to conventional slow evaporation or freeze drying. This parameter change in drying method and temperature control minimizes degradation while achieving solid form isolation of the compound
Solution Approach 2:
The spray drying process rapidly converts the solution to solid form in a short time, skipping through the prolonged drying period that causes degradation in conventional methods. The rapid atomization and quick drying prevent significant decomposition during the isolation process
2Reliability
If spray drying is used to obtain solid compounds, then degradation is minimized and high purity is achieved, but the process parameters must be precisely controlled
Solution Approach 1:
The patent establishes specific parameter ranges for spray drying (temperature 65-105°C, concentration 2-30% w/w, pH 7.6-9) that optimize both product stability and process control. These defined parameters make the complex spray drying process reliable and reproducible
Solution Approach 2:
The patent implements pH control during the spray drying process to maintain stability within the optimal range (pH 7.6-9). This feedback control ensures that the compound remains stable while achieving consistent high purity results across production batches
3Productivity
If high concentration solutions are used for spray drying, then productivity is improved, but degradation increases and purity decreases
Solution Approach 1:
The patent identifies an optimal concentration range (2-30% w/w, preferably 3-5% w/w) that balances productivity with purity. This parameter optimization allows efficient production while maintaining high purity by preventing degradation that occurs at higher concentrations
4Productivity
If spray drying is implemented at industrial scale, then large scale production is achieved, but process optimization becomes more difficult
Solution Approach 1:
The spray drying process parameters established in the patent (temperature 65-105°C, concentration 2-30% w/w, pH 7.6-9) are universally applicable to multiple 21-disodium phosphate compounds including betamethasone, dexamethasone, and prednisolone derivatives. This universality simplifies industrial scale-up by using the same optimized process for different compounds
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 process effectively prevents degradation and contamination, yielding high-purity amorphous solid compounds that comply with pharmacopoeial standards, suitable for large-scale industrial production and pharmaceutical use.
Implementation Method 1
spray drying a solution containing compound of formula [I]
Data Source
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AI summary
A process for obtaining 21-disodium phosphate pregnane derivative compounds of formula (I), wherein X=R=H or X=F and R=a-CH3 or X=F and R=ß-CH3: comprises spray drying a solution comprising compound of formula (I).