Solubility of vitamin d
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Solubility of Vitamin D: Insights from Recent Research
Solubility of Vitamin D3 in Various Solvents
Solubility in Mono Solvents
Vitamin D3, a fat-soluble vitamin, exhibits varying solubility in different mono solvents. Research has shown that vitamin D3 is practically insoluble in water, with a mole fraction solubility of 1.03 × 10⁻⁶ at 298.2 K1. In contrast, it is very soluble in organic solvents such as Transcutol® (4.03 × 10⁻¹), isopropanol (2.45 × 10⁻¹), ethyl acetate (1.95 × 10⁻¹), and ethanol (1.77 × 10⁻¹) at the same temperature1. These findings indicate that vitamin D3's solubility is significantly higher in organic solvents compared to water.
Solubility in Organic Solvents
Further studies have measured the solubility of vitamin D3 in six organic solvents, revealing a descending order of solubility: propan-1-ol > ethanol > ethyl ethanoate > propan-2-one > methanol > ethanenitrile. The highest solubility was observed in propan-1-ol (0.193 mole fraction at 273.2 K), while the lowest was in ethanenitrile (7.61 × 10⁻⁵ mole fraction at 248.2 K)3. This data underscores the variability in solubility depending on the solvent used.
Solubility in Transcutol® and Water Mixtures
An environmentally benign HPLC-UV method has been developed to measure the thermodynamic solubility of vitamin D3 in Transcutol® and water mixtures. The highest solubility was found in neat Transcutol® (4.04 × 10⁻¹ mole fraction at 298.2 K), while the lowest was in neat water (1.97 × 10⁻⁷ mole fraction at 273.2 K)2. This method provides a reliable way to assess vitamin D3 solubility in mixed solvent systems.
Thermodynamic Analysis of Solubility
Endothermic and Entropy-Driven Dissolution
Thermodynamic analysis of vitamin D3 solubility data indicates that the dissolution process is endothermic and entropy-driven across all solvents studied1 2. This means that the solubility of vitamin D3 increases with temperature, and the process is driven by an increase in disorder or randomness in the system.
Enhancing Solubility and Bioavailability
Use of Solubilizing Agents
The limited solubility of vitamin D3 in water poses challenges for its bioavailability. Various solubilizing agents have been evaluated to improve the solubility and stability of vitamin D3 in different formulations. For instance, alpha-lactalbumin has been identified as a promising carrier for vitamin D3, enhancing its solubility and protecting it from degradation7. Similarly, β-lactoglobulin-based coagulum has been shown to significantly increase the water solubility and stability of vitamin D3, leading to improved bioavailability in vivo9.
Protein-Polysaccharide Complexes
Protein-polysaccharide complexes, such as those formed between β-lactoglobulin and cress seed mucilage, have been used to encapsulate vitamin D3. These complexes protect vitamin D3 in acidic environments and facilitate its sustained release in simulated intestinal fluid, thereby enhancing its bioavailability10.
Conclusion
The solubility of vitamin D3 varies significantly across different solvents, with organic solvents generally providing higher solubility compared to water. Thermodynamic analyses reveal that the dissolution of vitamin D3 is endothermic and entropy-driven. To address the challenges of low water solubility and improve bioavailability, various solubilizing agents and encapsulation techniques have been explored, showing promising results in enhancing the stability and bioavailability of vitamin D3. These advancements hold potential for improving the efficacy of vitamin D3 supplements and formulations.
Sources and full results
Most relevant research papers on this topic
Solubility and thermodynamic function of vitamin D3 in different mono solvents
Vitamin D3 is practically insoluble in water, sparingly soluble in DMSO, PG, and PEG-400, and very soluble in ethanol, IPA, EA, 1-butanol, 2-butanol, and Transcutol®.
An environmentally benign HPLC-UV method for thermodynamic solubility measurement of vitamin D3 in various (Transcutol + water) mixtures
The developed HPLC-UV method effectively measures vitamin D3's thermodynamic solubility in various Transcutol® + water mixtures, with high accuracy and robustness.
Solubility of Vitamin D3 in Six Organic Solvents at Temperatures from (248.2 to 273.2) K
Vitamin D3's solubility in organic solvents decreases from propan-1-ol to methanol, with the maximum mole fraction solubility in propan-1-ol at 273.2 K.
Evaluation of solubilizing agents for 25-hydroxy-vitamin D3 immunoassays.
Solubilizing agents are essential for sensitive and reproducible 25(OH)D3 immunoassays, improving the overall vitamin D status measurement.
VALIDATION OF ANALYTICAL METHOD FOR THE DISSOLUTION TEST OF VITAMIN D3 5000 IU CHEWABLE TABLETS WITH HPLC AND STABILITY TESTING
The validation of the analytical method for dissolution of vitamin D3 chewable tablets with HPLC has met the acceptance criteria from ICH and USP.
Evaluation of vitamin D bioaccessibility and mineral solubility from test meals containing meat and/or cereals and/or pulses using in vitro digestion.
Chickpeas decrease vitamin D bioaccessibility and mineral solubility in meals, but their presence is compensated for by vitamin D being more stable in plant-based meals than beef-based meals.
Alpha-lactalbumin: A new carrier for vitamin D3 food enrichment
Alpha-lactalbumin can be a suitable carrier for vitamin D3 in low-fat food and non-alcohol drinks, enhancing its bioavailability and increasing its bioavailability.
Highly CitedSimulation of Physicochemical and Pharmacokinetic Properties of Vitamin D3 and Its Natural Derivatives
Lipophilicity and solubility significantly impact oral absorption of vitamin D3 derivatives, with calcitroic acid, 1,23S,25-trihydroxy-24-oxo-vitamin D3, and (23S,25R)-1,25-dihydroxyvitamin D3-26,23-lac
Improved bioavailability of vitamin D3 using a β-lactoglobulin-based coagulum.
The -lactoglobulin-based coagulum significantly enhances vitamin D3's bioavailability, stability, and uptake in rats by increasing its water solubility, long-term storage, and UV-light stability.
Non-RCT
Animal StudyVitamin D3 cress seed mucilage -β-lactoglobulin nanocomplexes: Synthesis, characterization, encapsulation and simulated intestinal fluid in vitro release.
Cress seed mucilage--lactoglobulin nanocomplexes effectively retain vitamin D3 at acidic pH levels and induce sustained release, offering practical advantages for vitamin delivery in food and pharmaceutical sectors.
In Vitro Study