Comparative Bioavailability Study of a New Vitamin D3 Orodispersible Film Versus a Marketed Oral Solution in Healthy Volunteers

Abstract

Background and Objective An orally disintegrating film (ODF) formulation of vitamin D3 that dissolves rapidly in the mouth without drinking or chewing may be a worthwhile alternative to currently available drug products for therapeutic vitamin D supplementation. This study aimed to compare the bioavailability of a single dose of a vitamin D3 25000 I.U. ODF with those of a marketed oral vitamin D3 preparation in healthy subjects. Methods This Phase 1, randomised, parallel-group, open-label study compared the pharmacokinetics of calcifediol [25(OH)D3], the precursor of bioactive vitamin D3, after a single dose of a new vitamin D3 25,000 I.U. ODF with those of a Reference formulation (vitamin D3 25000 I.U./2.5 mL oral solution) in healthy adult subjects using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. The primary objective was bioavailability under fed conditions, defined as maximum plasma concentration (C max ) of 25(OH)D3 and area under the concentration-time curve from time zero to time t, the last quantifiable concentration (AUC 0− t ). The pharmacokinetics of 25(OH)D3 were also evaluated following the ODF administration under fasting conditions. Subjects were randomised to receive a single dose of the vitamin D3 25000 I.U. ODF or the Reference oral solution under fed conditions or the vitamin D3 ODF under fasting conditions. Results Forty-eight healthy subjects were randomised and completed the study. Overall, the pharmacokinetic profile was very similar across the three treatment groups, and bioavailability did not significantly differ among treatments. Under fed conditions, mean 25(OH)D3 plasma values for C max were 6.68 ± 2.03 versus 6.61 ± 2.62 ng/mL for the Test versus Reference formulations. Corresponding values for AUC 0− t were 2364.80 ± 1336.97 versus 2150.52 ± 1622.76 ng/mL × h. Mean C max was slightly lower (6.68 ± 2.03 vs 7.23 ± 1.48 ng/mL) and the time to reach peak concentration was delayed (144 h [36–312] versus 42 h (2–480]) with the ODF under fed versus fasting conditions ( p = 0.0371). The point estimates and 90 % CIs of the Test fed /Reference fed ratios of the geometric means showed that the bioavailability of exogenous 25(OH)D3 was, both in rate and extent of absorption, slightly higher with the vitamin D3 ODF than the vitamin D3 oral solution under the administration conditions recommended for the vitamin D3 oral solution. Palatability and ease of use of the ODF were satisfactory. Conclusion The new ODF 25000 I.U. formulation provided a valuable alternative to the marketed oral solution for therapeutic vitamin D supplementation, with a bioavailability that was slightly higher ...

Recent progress in orodispersible films‐mediated therapeutic applications: A review

“…The ODFs with the loading of vitamin D3 showed a slightly higher in rate (C max ) and extent of absorption (AUC 0−t and AUC 0–∞ ) than vitamin D3 oral solution. Therefore, these results proved that ODFs could be a promising alternative to the commercial vitamin D3 oral solution 66 …”

“…Therefore, these results proved that ODFs could be a promising alternative to the commercial vitamin D3 oral solution. 66 An acceptable taste is important for ensuring patient acceptability and compliance. The taste should be taken into consideration when preparing formulations, especially for pediatrics, who are more sensitive to bitterness.…”

Orodispersible Film (ODF) Platform Based on Maltodextrin for Therapeutical Applications

“…Films based on maltodextrin were demonstrated to be chemically and microbiologically stable [ 3 , 45 ]. For a sildenafil ODF containing PVAc, the mechanical properties were evaluated in a stability study; at the end of the accelerated stability study (6 months), and during the intermediate and long-term stability study (24 months), tensile strength and elongation at break were calculated.…”

“…Forty-eight subjects were randomized to receive a single dose of vitamin D3 25,000 IU ODF made of maltodextrin under fasting conditions, a single dose of vitamin D3 ODF under fed conditions or a single dose of vitamin D3 25,000 IU oral solution [ 45 ]. The results support the conclusion that the bioavailability of exogenous calcifediol following a single 25,000 IU ODF intake is comparable to or better than an equivalent dose of the reference oral solution when administered under the same (fed) conditions in terms of both rate (Cmax) and extent (AUC0-t = 72 h) of absorption.…”

Gastro-Resistant Microparticles Produced by Spray-Drying as Controlled Release Systems for Liposoluble Vitamins

“…The term “Vitamin D” refers to both ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) [ 8 ]. Cholecalciferol has an increasingly acknowledged role in the development of several autoimmune diseases, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease [ 9 ].…”