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  • Characterization of a riboflavin non-aqueous nanosuspension prepared by bead milling for cutaneous application.

Characterization of a riboflavin non-aqueous nanosuspension prepared by bead milling for cutaneous application.

Chemical & pharmaceutical bulletin (2015-03-10)
Takayuki Sato, Hiroyuki Takeuchi, Takanobu Sakurai, Kensuke Tanaka, Kota Matsuki, Kenjirou Higashi, Kunikazu Moribe, Keiji Yamamoto
ABSTRACT

The purpose of this study was to characterize the non-aqueous nanosuspension of a hydrophilic drug prepared by bead milling for cutaneous application. Riboflavin was used as the model hydrophilic drug. The non-aqueous nanosuspensions were prepared by grinding riboflavin with zirconia beads using eight non-aqueous bases. The mean particle size of riboflavin in the suspensions ranged from 206 to 469 nm, as determined by the dynamic light scattering method. Among the well-dispersed samples, riboflavin nanosuspension prepared in oleic acid was selected for evaluation of the drug permeability through rat skin. The cumulative amount and permeation rate of riboflavin from the nanosuspension were approximately three times higher than those for unprocessed riboflavin in oleic acid. Fluorescence imaging of the riboflavin nanosuspension suggested improved penetration of riboflavin into the stratum corneum. Furthermore, the addition of polysorbate 65 or polyglyceryl-6 polyricinoleate to the nanosuspension prepared in oleic acid markedly improved the riboflavin dispersibility. These results show that the preparation of a nanosuspension in a non-aqueous base by bead milling is one of the simple methods to improve the skin permeability of hydrophilic drugs.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Oleyl alcohol, ≥99% (GC)
Sigma-Aldrich
Zirconium(IV) oxide, 99.99% trace metals basis (purity excludes ~2% HfO2)
SAFC
Oleyl alcohol, analytical standard
Riboflavin for peak identification, European Pharmacopoeia (EP) Reference Standard
Supelco
Triacetin, analytical standard
Riboflavin, European Pharmacopoeia (EP) Reference Standard
USP
Triacetin, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Propylene carbonate, ReagentPlus®, 99%
USP
Riboflavin, United States Pharmacopeia (USP) Reference Standard
Supelco
Triacetin, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Propylene carbonate, suitable for HPLC, 99.7%
Supelco
Riboflavin (B2), analytical standard
Supelco
Riboflavin, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Zirconium(IV) oxide, powder, 5 μm, 99% trace metals basis
Sigma-Aldrich
Triacetin, 99%, FCC, FG
Sigma-Aldrich
Oleyl alcohol, technical grade, 85%
Sigma-Aldrich
Triacetin, 99%
Sigma-Aldrich
Propylene carbonate, anhydrous, 99.7%
Sigma-Aldrich
Zirconium(IV) oxide, nanopowder, <100 nm particle size (TEM)
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(−)-Riboflavin, from Eremothecium ashbyii, ≥98%
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(−)-Riboflavin, meets USP testing specifications
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(−)-Riboflavin, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥98%
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Oleic acid, suitable for cell culture, BioReagent
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Oleic acid, meets analytical specification of Ph, Eur., 65.0-88.0% (GC)
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Oleic acid, natural, FCC
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Oleic acid, technical grade, 90%
Supelco
Oleic acid, Selectophore, ≥99%
Oleic acid, European Pharmacopoeia (EP) Reference Standard
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Zirconium(IV) oxide, nanoparticles, dispersion, <100 nm particle size (BET), 5 wt. % in H2O
Sigma-Aldrich
Zirconium(IV) oxide, nanoparticles, dispersion, <100 nm particle size (BET), 10 wt. % in H2O