Enhanced dissolution rate and oral bioavailability of simvastatin nanocrystal prepared by sonoprecipitation.
BACKGROUND
Simvastatin is classified as a Biopharmaceutics Classification System (BCS) Class-II compound with a poor aqueous solubility and an acceptable permeability through biomembranes. The strategy of increasing the in vitro dissolution has the potential to enhance the oral bioavailability when using nanosized crystalline drugs.


OBJECTIVE
The aim of this article was to prepare simvastatin nanocrystals to enhance its dissolution rate and bioavailability by exploiting sonoprecipitation.


METHODS
Injecting 0.50% (w/v) methanol solution of simvastatin into 0.20% (w/v) water solution of F68 under sonication amplitude of 400 W and processing temperature of 3°C.


RESULTS
Simvastatin nanocrystal with average diameter of 360 ± 9 nm could be obtained. X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) confirmed the decreased crystallinity of nanoparticles stabilized by F68. The results of in vitro study demonstrated that the saturation solubility and dissolution rate of simvastatin nanocrystals were enhanced by 1 fold and 4 fold respectively, compared with crude simvastatin and the dissolution rate improved with the decrease in particle size. The C(max) and AUC((0-24 h)) values of simvastatin nanocrystal group were approximately 1.50-fold and 1.44-fold greater than that of simvastatin nanocrystal group, respectively. Additionally, the T(max) of simvastatin nanocrystal group was 1.99 h, comparing to 2.88 h of reference group.


CONCLUSIONS
Sonoprecipitation method can produce small and uniform simvastatin nanocrystals with an improved saturation solubility, dissolution rate and oral bioavailability.
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China.
Tongying
T
Jiang
Ning
N
Han
Buwen
B
Zhao
Yuling
Y
Xie
Siling
S
Wang
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D011232:Chemical Precipitation; D000432:Methanol / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000737:chemistry* / Q000493:pharmacokinetics*; D012995:Solubility; D013010:Sonication / Q000379:methods; D013696:Temperature; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods
D014867:Water; D019821:Simvastatin; D000432:Methanol