Vitamin D3, also known as Cholecalciferol, is an important fat-soluble vitamin and pharmaceutical active ingredient used in vitamin supplementation, nutritional formulations and pharmaceutical products designed to support calcium and phosphorus metabolism. Cholecalciferol is the naturally occurring form of vitamin D3 and is widely used in pharmaceutical, nutraceutical and dietary formulations.
Vitamin D3 has the CAS Number 67-97-0, molecular formula C27H44O, and molecular weight 384.64 g/mol. It is chemically classified as a secosteroid and is structurally related to cholesterol. Vitamin D3 is produced commercially through photochemical conversion of 7-dehydrocholesterol followed by purification and crystallization.
Cholecalciferol is a white to almost white crystalline material and is practically insoluble in water. It is freely soluble in ethanol and soluble in fatty oils and selected organic solvents. Because Vitamin D3 is sensitive to oxygen, heat and light, pharmaceutical-grade material requires appropriate protection during processing, packaging and storage.
Vitamin D3 is a secosteroid compound formed naturally in the skin following exposure to ultraviolet-B radiation. Industrially produced Cholecalciferol is purified and standardized for pharmaceutical and nutritional applications.
The molecular structure contains a steroid-derived ring system that has undergone cleavage, giving vitamin D3 its characteristic secosteroid structure. The compound contains one hydroxyl group and an extended conjugated triene system.
The pharmaceutical substance is optically active and has a characteristic specific rotation of approximately +105° to +112° under the applicable pharmacopoeial test conditions.
Vitamin D3 API is widely used in pharmaceutical and nutritional formulations, including:
Vitamin D3 is used to help maintain normal calcium and phosphate homeostasis and supports normal bone mineralization.
Vitamin D3 itself is biologically inactive or relatively inactive compared with its hydroxylated metabolites. Following absorption, it undergoes metabolic conversion in the liver to 25-hydroxyvitamin D3 (calcidiol) and subsequently in the kidneys and other tissues to biologically active vitamin D metabolites, including 1,25-dihydroxyvitamin D3 (calcitriol).
These metabolites participate in the regulation of calcium and phosphate metabolism and are important for normal bone and mineral physiology.
Cholecalciferol is generally supplied as a white or almost white crystalline powder or crystals.
Important characteristics include:
Vitamin D3 is sensitive to light, oxygen and heat. Solutions may undergo isomerization and degradation if not appropriately protected.
Vitamin D3 is commonly expressed in International Units (IU) because of its biological activity.
1 microgram of Cholecalciferol corresponds to 40 IU of vitamin D3 activity.
Therefore:
1 mg Cholecalciferol = 40,000 IU
A nominal pharmaceutical-grade Vitamin D3 material may therefore be expressed in terms of both chemical assay and biological potency.
Cholecalciferol has an established USP monograph. The USP definition specifies NLT 97.0% and NMT 103.0% Cholecalciferol.
The USP identification procedure includes infrared absorption, ultraviolet absorption at approximately 265 nm, a color reaction and chromatographic identification. The USP also specifies specific optical rotation of +105° to +112°.
The European Pharmacopoeia/British Pharmacopoeia specification commonly uses an assay range of approximately 97.0–102.0% for Cholecalciferol, with appropriate control of related substances.
Vitamin D3 is susceptible to isomerization and degradation, particularly when exposed to light, heat and oxygen. Important related compounds can include pre-cholecalciferol, trans-cholecalciferol and 7-dehydrocholesterol-related substances.
Chromatographic control is therefore important for pharmaceutical-grade Cholecalciferol.
The USP chromatographic procedure specifically controls separation of trans-cholecalciferol, pre-cholecalciferol and cholecalciferol, demonstrating the importance of related-substance control.
Vitamin D3 should be protected from:
Pharmacopoeial information recommends storage in hermetically sealed containers under nitrogen, in a cool location protected from light. Refrigerated storage around 2–8°C is commonly used for pharmaceutical-grade crystalline Cholecalciferol.
Vitamin D3 API is suitable for pharmaceutical manufacturers, nutraceutical companies and formulation developers requiring high-purity Cholecalciferol for tablets, capsules, soft gels, oral liquids, multivitamin preparations and calcium-vitamin D formulations.
Swapnroop Drugs & Pharmaceuticals provides Vitamin D3 API for pharmaceutical formulation, nutritional product development, research and bulk manufacturing requirements, subject to applicable quality and regulatory specifications.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 97.0–103.0% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Specific Rotation | +105° to +112° |
| Melting Point | 83–86°C |