title: Fabrication of carvedilol nanosuspensions through the anti-solvent precipitation-ultrasonication method for the improvement of dissolution rate and oral bioavailability.
abstract: The present study aims to prepare carvedilol (CAR) nanosuspensions using the anti-solvent precipitation-ultrasonication technique to improve its dissolution rate and oral bioavailability. Alpha-tocopherol succinate (VES) was first used as a co-stabilizer to enhance the stability of the nanosuspensions. The effects of the process parameters on particle size of the nanosuspensions were investigated. The optimal values of the precipitation temperature, power inputs, and the time length of ultrasonication were selected as 10°C, 400 W, and 15 min, respectively. Response surface methodology based on central composite design was utilized to evaluate the formulation factors that affect the size of nanosuspensions, i.e., the concentration of CAR and VES in the organic solution, and the level of sodium dodecyl sulfate in the anti-solvent phase, respectively. The optimized formulation showed a mean size of 212 ± 12 nm and a zeta potential of -42 ± 3 mV. Scanning electron microscopy revealed that the nanosuspensions were flaky-shaped. Powder X-ray diffraction and differential scanning calorimetry analysis confirmed that the nanoparticles were in the amorphous state. Fourier transform infrared analysis demonstrated that the reaction between CAR and VES is probably due to hydrogen bonding. The nanosuspension was physically stable at 25°C for 1 week, which allows it to be further processing such as drying. The dissolution rate of the nanosuspensions was markedly enhanced by reducing the size. The in vivo test demonstrated that the C(max) and AUC(0-36) values of nanosuspensions were approximately 3.3- and 2.9-fold greater than that of the commercial tablets, respectively.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, People's Republic of China. liudandan1124@126.com
authors.forename: Dandan
authors.initials: D
authors.lastname: Liu
authors.forename: Heming
authors.initials: H
authors.lastname: Xu
authors.forename: Baocheng
authors.initials: B
authors.lastname: Tian
authors.forename: Kun
authors.initials: K
authors.lastname: Yuan
authors.forename: Hao
authors.initials: H
authors.lastname: Pan
authors.forename: Shilin
authors.initials: S
authors.lastname: Ma
authors.forename: Xinggang
authors.initials: X
authors.lastname: Yang
authors.forename: Weisan
authors.initials: W
authors.lastname: Pan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002227:Carbazoles / Q000138:chemical synthesis* / Q000378:metabolism; D000077261:Carvedilol; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011412:Propanolamines / Q000138:chemical synthesis* / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D012997:Solvents / Q000737:chemistry* / Q000378:metabolism; D013535:Suspensions / Q000737:chemistry / Q000378:metabolism; D014465:Ultrasonics / Q000379:methods*; D014961:X-Ray Diffraction
chemical_list: D002227:Carbazoles; D011412:Propanolamines; D012997:Solvents; D013535:Suspensions; D000077261:Carvedilol