Stabilized 1,25-Dihydroxyvitamin D2 Crystallization
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Solution Overview
Problem
Activated vitamin D compounds, such as 1,25-dihydroxyvitamin D2, are chemically unstable under light and oxygen exposure and have poor storage stability at higher temperatures, which complicates their use in pharmaceutical formulations.
Innovation Solution
A method involving crystallization from an acetone/water mixture is used to produce a stabilized 1,25-dihydroxyvitamin D2 that is free of methyl formate, enhancing its stability and purity, with a high yield and minimal residual solvents, suitable for pharmaceutical formulations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If 1,25-dihydroxyvitamin D2 is stored under conventional conditions, then it can be used in pharmaceutical formulations, but it degrades rapidly under light and oxygen exposure and at higher temperatures
Solution Approach 1:
The patent removes the harmful methyl formate solvent from the crystallization process and replaces it with alternative solvents. This extraction of the harmful element eliminates the source of degradation while preserving the stabilizing effect of crystallization, thereby resolving the contradiction between storage stability and chemical stability
Solution Approach 2:
The patent changes the crystallization parameters by using different solvents (ethyl formate, n-butyl formate, isopropyl alcohol, ethyl acetate, n-butyl acetate) and adjusting crystallization conditions. These parameter changes produce a stabilized polymorph that resists degradation from light, oxygen, and heat, thus improving both storage and chemical stability simultaneously
2Manufacturing precision
If methyl formate is used for crystallization, then 1,25-dihydroxyvitamin D2 can be purified, but residual methyl formate accelerates degradation
Solution Approach 1:
The patent extracts and eliminates methyl formate from the crystallization process. By removing this harmful solvent and replacing it with alternatives that do not leave degrading residues, the patent achieves both high purity through crystallization and improved storage stability without the harmful side effect of residual solvent-induced degradation
Solution Approach 2:
The patent employs disposable alternative solvents (ethyl formate, n-butyl formate, isopropyl alcohol, ethyl acetate, n-butyl acetate) that can be completely removed or left as harmless residues. These solvents serve their purification purpose and are then discarded or remain as stable residues, unlike methyl formate which continuously degrades the product during storage
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 stabilized 1,25-dihydroxyvitamin D2 exhibits improved storage stability, maintaining high purity even at elevated temperatures and during prolonged storage, making it suitable for modern therapy formulations.
Implementation Method 1
Another aspect of the disclosure provides an efficient method for crystallizing 1,25-dihydroxyvitamin D2 to produce a stabilized 1,25-dihydroxyvitamin D2 at relatively high yield, the method including crystallization from an acetone/water mixture.
Implementation Method 2
The stabilized 1,25-dihydroxyvitamin D2 exhibits improved storage stability, maintaining high purity even at elevated temperatures and during prolonged storage
Data Source
AI summary
A stabilized 1,25-dihydroxyvitamin D2 composition which is particularly well suited for pharmaceutical formulations, pharmaceutical formulations of the 1,25-dihydroxyvitamin D2 composition, and a method of making the purified composition by purifying a crude 1,25-dihydroxyvitamin D2 from acetone/water, are disclosed.