Formulation study of topically applied O/W lotion containing vitamin D3 derivative, focusing on skin permeability of the drug

Abstract

Permeation of 22-oxacalcitriol-1α, 25-dihydroxyvitamin D₃ (OCT) through excited hairless mouse skin was determined after application of OCT as solutions and O/W lotions consisted of different polarities of solvents: medium-chain fatty acid triglyceride (MCT), myristate isopropyl (IPM), 1,3-butylene glycol (1,3-BG), and propylene glycol (PG). OCT concentration in skin was also followed after applying these formulations. A two-layer diffusion model was composed to analyze dermatopharmacokinetic profiles of OCT for each vehicle. In the OCT solutions, skin permeation profile of OCT differed depending on solvent polarity. The O/W lotion with a high MCT content led to a low amount of OCT in skin. On the other hand, the O/W lotion with a high 1,3-BG content led to a high amount of OCT in skin. This dermatopharmacokinetic analysis indicated that addition of MCT to the formulation decreases the skin/vehicle partition coefficient of OCT and increases the diffusion coefficient of OCT in skin. However, the opposite effects on these two parameters were found in the case of 1,3-BG. Thus, skin permeability of OCT differed depending on the solvents used in the formulation. These results indicate that skin permeability of OCT is influenced by the physicochemical properties (i.e. polarity) of OCT, solvent, and skin. Our findings on the solvent effects of the skin permeability of OCT are thus useful for designing topical drug formulation, especially in aiming for bioequivalent dosage formulas.

Keywords::

• Topical formulation
• O/W lotion
• skin permeation
• partition
• diffusion
• solvent polarity

Acknowlegements

The authors are very grateful to Drs. H. Todo and N. Hada at the Faculty of Pharmaceutical Sciences, Josai University for their useful advice. We also thank K. Tujimura, T. Paku, Y. Ueda, S. Nomura, and J. Takahara of Maruho Co., Ltd., Kyoto R&D Center for their assistance with practical experiments.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.