Production of griseofulvin nanoparticles via wet-grinding method / Eka Giyanti Puteri Ramli

Poorly water soluble drugs pose formulation problem and low oral bioavailability. Size reduction is among the several approaches to improve the solubility of such drugs. Wet grinding is a relatively new technology used to reduce the particle sice down to submicron range. Griseofulvin a BCS II Class model drug was used to assess the feasibility of the above method to reduce the particle size to nanoscale with narrower distribution of particle size. Different factors such as type of the surfactants, concentration of surfactants, grinding speed, grinding time and the size of the grinding media (grinding beads) was varied to find the optimized.conditions to achieve the desired particle size and size distribution of the griseofulvin particles. The lowest mean particle size of 123 ± 0.0 nm for griseofulvin was accomplished with 5% w/v blend of 1.65% w/v of Tween 80 and 3.35% w/v of Span 80 at 1200 rpm using grinding media of 1 mm in diameter for 60 minutes followed by using 0.2 mm in diameter for 90 minutes (total 150 minutes). The next procedure considered the storage stability of nanosuspension. The type and concentration of stabilizers were varied. This study focused on the particle size growth control (Oswald ripening) during storage (monthly up to 3 months). The results showed that manitol 3% w/v used as a stabilizer could maintain the particle size at 158 nm with uniformity of 0.336 at 3 months storage condition (room temperature). In vitro dissolution rate of griseofulvin was significantly increased by reduction of particle size. Griseofulvin of different particle sizes rapidly dissolved in different dissolution media. The results showed that griseofulvin in nanosize almost 100 % dissolved in the aqueous solution after 120 minutes. The oral bioavailability of griseofulvin of different particle size was found to be significantly increased by reduction of particle size. The results showed that griseofulvin in nanosized form had greater bioavailability compared to the macrosized and microsized forms. The AUC(o-24), Cmax, and Tmax of nanosized griseofulvin after oral administration were greater than the macrosized and microsized griseofulvin. The AUC(o-24) of nanosized griseofulvin was one (1) fold greater than the microsized form and three (3) folds greater than the macrosized griseofulvin. The Cmax of nanosized griseofulvin was one (1) fold of the macrosized form and two (2) folds of the microsized form. The Tmax of the three (3) suspensions were not statistically significantly different. The tissue distribution study showed that a higher concentration of griseofulvin in tissues (kidney, liver, skin and brown adipose) was achieved by the nanosized griseofulvin than the macrosized griseofulvin. After two (2) hours of oral administration, the hightest concentration of nanosized griseofulvin was found in the liver. This study shows that wet grinding is a possible method for the preparation of griseofulvin nanoparticles for improved oral bioavailability of this antibiotic.