Characterization of a riboflavin non-aqueous nanosuspension prepared by bead milling for cutaneous application.
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.
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675; Pharmaceutics, Pharmaceutical Science Laboratories, Research Headquarters, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan. takayu-satou@so.taisho.co.jp
Takayuki
T
Sato
Hiroyuki
H
Takeuchi
Takanobu
T
Sakurai
Kensuke
K
Tanaka
Kota
K
Matsuki
Kenjirou
K
Higashi
Kunikazu
K
Moribe
Keiji
K
Yamamoto
D000818:Animals; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D019301:Oleic Acid / Q000737:chemistry; D061848:Optical Imaging; D010316:Particle Size; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012256:Riboflavin / Q000737:chemistry / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D012995:Solubility; D013535:Suspensions / Q000737:chemistry*; D015040:Zirconium / Q000737:chemistry
D004337:Drug Carriers; D013535:Suspensions; D019301:Oleic Acid; D015040:Zirconium; C028541:zirconium oxide; D012256:Riboflavin