An open-label, randomized, crossover study to evaluate the bioavailability of nanoemulsion versus conventional fat-soluble formulation of cholecalciferol in healthy participants

Raman Kumar Marwaha; Manish Verma; Ajit Walekar; Rakesh Sonawane; Chirag Trivedi

doi:10.1016/j.jor.2022.10.017

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. doi: 10.1016/j.jor.2022.10.017. eCollection 2023 Jan.

Authors

Raman Kumar Marwaha¹, Manish Verma², Ajit Walekar³, Rakesh Sonawane², Chirag Trivedi³

Affiliations

¹ Consultant Endocrinologist and President, Society of Endocrine Health Care for Elderly, Adolescents and Children (SEHEAC), 92E/I, Ground Floor, Munirka Market, New Delhi, 110067, India.
² Medical Affairs, CHC, Sanofi India Limited, Sanofi House, CTS No.117-B, L&T Business Park, Saki Vihar Road, Powai, Mumbai, 400072, India.
³ Clinical Study Unit, Sanofi Healthcare India Private Limited, Sanofi House, CTS No.117-B, L&T Business Park, Saki Vihar Road, Powai, Mumbai, 400072, India.

Abstract

Background: Nanoemulsion preparations of cholecalciferol available in the market claim to have better bioavailability than the conventional fat-soluble cholecalciferol. However, limited data are available in humans for such preparations. We, therefore, compared the relative bioavailability of two formulations of 60,000 IU cholecalciferol (nanoemulsion oral solution, water-miscible vitamin D3 [test] vs soft gelatin capsules [reference]) in healthy adult participants.

Methods: In this randomized, open-label, two sequence, single-dose, two-way crossover study (CTRI/2018/05/013839), Indian participants aged 18-45 years received single dose of nanoemulsion and capsule formulations, under fasting conditions. Blood samples collected over 120 h were assessed to determine cholecalciferol concentrations. Pharmacokinetic parameters (area under the concentration-time curve up to 120 h [AUC_0-120h], maximum observed drug concentration [C_max], time to reach maximum drug concentration [T_max], terminal half-life [T_½el], and terminal elimination rate constant [K_el]) were estimated using baseline corrected data and analyzed using analysis of variance.

Results: Among the 24 eligible participants, the relative bioavailability of nanoemulsion was significantly higher than the capsules by 36% (p = 0.0001) based on AUC_0-120h. Similarly, C_max of the nanoemulsion was significantly higher by 43% (p = 0.0001) than that of the capsules. The intra-participant variability for AUC_0-120h and C_max were 23.22% and 26.51%, respectively. The T_max, T_½el, and K_el were comparable for both the formulations. No adverse effects were noted with either of the two formulations.

Conclusions: Nanoemulsion oral solution of cholecalciferol showed a greater bioavailability compared with soft gelatin capsules, under fasting conditions, in healthy human participants.

Keywords: Absorption; Area under curve; Biological availability; Lipid digestion; Nanotechnology; Therapeutic equivalency; Vitamin D deficiency.