Preparation of griseofulvin nanoparticle suspension by high-pressure homogenization and preservation of the suspension with saccharides and sugar alcohols.
OBJECTIVE
We have attempted to micronize drug particles with a particle size of less than 100 nm and maintain the particle size of their suspension to improve the solubility and bioavailability of poorly water-soluble drugs. Furthermore, the method of freeze-drying nanoparticles was applied to maintain particulate nature of nanoparticles containing various saccharides and sugar alcohols for a long time.


METHODS
Griseofulvin (GF)-lipid nanoparticle suspension is prepared using GF and a lipid by high-pressure homogenization. The particle size of the obtained GF-lipid nanoparticle suspension is maintained constant by freeze-drying.


RESULTS
The mean particle size of GF-lipid nanoparticles prepared by high-pressure homogenization is approximately 60 nm. The mean particle size remains less than 100 nm for 1 month. The GF-lipid nanoparticle suspension containing xylitol, trehalose, or sucrose is freeze-dried to maintain the particulate nature. The mean particle size of the rehydrated suspension is lower than that of the rehydrated suspension containing erythritol or lactose. In particular, it is new knowledge to have found that an aggregation is minimized by adding xylitol which is sugar alcohol. The minimum concentration of xylitol, trehalose, and sucrose required to maintain a constant particle size by rehydration is 3%, 3%, and 5% (w/v), respectively.
Kamiya
Seitaro
S
Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki, Japan. kamiya@niu.ac.jp
Kurita
Takurou
T
Miyagishima
Atsuo
A
Arakawa
Masayuki
M
D000935:Antifungal Agents / Q000008:administration & dosage*; D001682:Biological Availability; D004355:Drug Stability; D004896:Erythritol / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D005612:Freeze Drying; D006118:Griseofulvin / Q000008:administration & dosage*; D007785:Lactose / Q000737:chemistry; D053758:Nanoparticles; D010316:Particle Size; D012995:Solubility; D013395:Sucrose / Q000737:chemistry; D013535:Suspensions; D014199:Trehalose / Q000737:chemistry; D014993:Xylitol / Q000737:chemistry
D000935:Antifungal Agents; D005079:Excipients; D013535:Suspensions; D006118:Griseofulvin; D013395:Sucrose; D014199:Trehalose; D007785:Lactose; D004896:Erythritol; D014993:Xylitol