Brief Review on Vitamin D Formulations: Spotlight on Nanoemulsion and Its Innovations

Deficiency and insufficiency of vitamin D is a global concern, affecting a vast proportion of the Indian population as well; with reportedly 85% suffering from vitamin D deficiency. (1) The role and acceptance of vitamin D supplementation are well-established, with diverse formulations available to cater to supplementation needs. (2) This article reviews these formulations to aid clinicians in making informed decisions when recommending them.

Vitamin D Formulations: An Overview

Vitamin D3 is highly sensitive to environmental stresses, such as oxidation, which diminishes its physiological benefits. It also exhibits poor water solubility and an oral bioavailability of about 44.8%. (3) Given these stability, solubility, absorption, and metabolism challenges, evolving methods like solid dispersion, solid lipid nanoparticles, self-emulsifying drug delivery systems (SEDDS), and nanoemulsification have become relevant for enhancing stability and bioavailability. (4)

Nanoemulsion Vitamin D: A Novel Formulation with Clinical Benefits

Nanoemulsions, colloidal particulate systems in the submicron size range (20–200 nm), act as carriers for drug molecules, promoting efficient delivery of micronutrients like vitamin D3. These systems offer enhanced stability, solubility, and absorption compared to conventional formulations. (5)

Nanoemulsion vs. Conventional Vitamin D Formulations: Indian Experience

A randomized, open-label, single-dose, crossover study compared the relative bioavailability of 60,000 IU cholecalciferol in two forms: nanoemulsion oral solution water-miscible vitamin D3 (test) versus soft gelatin capsules (reference) in 25 healthy Indian adults. The key findings included as follows: (6)

• Relative Bioavailability: Nanoemulsion showed 36% higher bioavailability (p=0.0001) based on AUC₀–₁₂₀h.
• Peak Concentration: Cmax of the nanoemulsion was 43% higher (p=0.0001).
• Intra-participant variability: AUC₀–₁₂₀h- 23.22% and Cmax: 26.51%, respectively.
• Safety: No adverse effects were noted in either formulation except mild pharyngitis in one participant.

These results indicated nanoemulsion oral solution water-miscible vitamin D3 showed a greater bioavailability compared with soft gelatin capsules under fasting conditions in healthy human participants.

Lipid Nanoparticle Innovations: Optimizing Vitamin D Absorption

Lipid nanoparticles facilitate increased drug absorption through three mechanisms: (7)

• Pre-Enterocyte Level: Solubilization of the active agent.
• Intra-Enterocyte Level: Chylomicron formation.
• Post-Enterocyte Level: Lymphatic drug transport.

Together, these mechanisms help amplify systemic and lymphatic transport, enhancing the absorption of lipid nanoparticle-based formulations.

Take-Home Messages

• Vitamin D supplementation plays a key role in addressing global vitamin D deficiencies and insufficiencies.
• All vitamin D formulations may not lead to similar benefits. Bioavailability and absorption are vital considerations when selecting vitamin D formulations.
• Nanoemulsion formulations offer enhanced stability and bioavailability compared to conventional forms. These formulations can be consumed directly with water, unlike fat-soluble vitamin D, which requires fat-based carriers for optimal absorption.
• Patent-protected technologies like Aqueol nanotechnology provide proven absorption advantages supported by clinical evidence, making them a superior option for consideration to address vitamin D insufficiency.

References:

1. Harinarayan CV, Akhila H, Shanthisree E. Modern India and Dietary Calcium Deficiency-Half a Century Nutrition Data-Retrospect-Introspect and the Road Ahead. Front Endocrinol (Lausanne). 2021 Apr 6;12:583654.

2. Marwaha RK, Dev T, Mittal A, Mani K, Narang A, Arora P, Singh A, Chadha A, Dang N, Goel M, Sharma VK, Sethuraman G. A randomized controlled trial comparing the efficacy of micellised and fat-soluble vitamin D3 supplementation in healthy adults. Br J Nutr. 2019 Apr;121(8):859-865.

3. Asfour MH, Abd El-Alim SH, Kassem AA, Salama A, Gouda AS, Nazim WS, Nashaat NH, Hemimi M, Abdel Meguid N. Vitamin D3-Loaded Nanoemulsions as a Potential Drug Delivery System for Autistic Children: Formulation Development, Safety, and Pharmacokinetic Studies. AAPS PharmSciTech. 2023 Feb 9;24(2):58

4. Gupta R, Behera C, Paudwal G, Rawat N, Baldi A, Gupta PN. Recent Advances in Formulation Strategies for Efficient Delivery of Vitamin D. AAPS PharmSciTech. 2018 Dec 17;20(1):11.

5. Khalid A, Arshad MU, Imran A, Haroon Khalid S, Shah MA. Development, stabilization, and characterization of nanoemulsion of vitamin D3-enriched canola oil. Front Nutr. 2023 Aug 24;10:1205200

6. Marwaha RK, Verma M, Walekar A, Sonawane R, Trivedi C. An open-label, randomized, crossover study to evaluate the bioavailability of nanoemulsion versus conventional fat-soluble formulation of cholecalciferol in healthy participants. J Orthop. 2022 Nov 4;35:64-68.

7. Poovi, Ganesan and Narayanasamy Damodharan. “Lipid nanoparticles: A challenging approach for oral delivery of BCS Class-II drugs.” Future Journal of Pharmaceutical Sciences (2018)