Physical-chemical properties of furosemide nanocrystals developed using rotation revolution mixer.
Recently, several approaches have been reported to improve the dissolution rate and bioavailability of furosemide, a class IV drug. However, to the best of our knowledge, none of them proposed nanocrystals. In the last decade, nanocrystals successfully addressed solubility issues by increasing surface area and saturation solubility, both leading to an increase in the dissolution rate of poor water soluble drugs. The preparation of furosemide nanocrystals was by a rotation revolution mixer method. Size distribution and morphology were performed using laser diffraction and scanning electron microscopy, respectively. In addition, differential scanning calorimetry, thermogravimetry, X-ray powder diffraction (XRD) and low frequency shift-Raman spectroscopy allowed investigating the thermal properties and crystalline state. Solubility saturation and intrinsic dissolution rate (IDR) studies were conducted. The thermal analysis revealed lower melting range for the nanocrystals comparing to furosemide. Moreover, a slight crystalline structure change to the amorphous state was observed by XRD and confirmed by low frequency shift Raman. The particle size was reduced to 231 nm with a polydispersity index of 0.232, a 30-fold reduction from the original powder. Finally, the saturation solubility and IDR showed a significant increase. Furosemide nanocrystals showed potential for development of innovative formulations as an alternative to the commercial products.
a Faculty of Pharmaceutical Sciences , University of São Paulo , São Paulo , São Paulo , Brazil.
Sávio Fujita
SF
Barbosa
b Thinky Corporation , Tokyo , Japan.
Takayuki
T
Takatsuka
c Course of Pharmacy, Department of Biochemistry , Institute of Biology, State University of Campinas , Campinas , São Paulo , Brazil , and.
Guilherme Diniz
GD
Tavares
a Faculty of Pharmaceutical Sciences , University of São Paulo , São Paulo , São Paulo , Brazil.
Gabriel Lima Barros
GL
Araújo
d Faculty of Pharmacy and Pharmaceutical Sciences , Katz Group-Rexall Centre for Pharmacy & Health Research, University of Alberta , Edmonton , Alberta , Canada.
Hui
H
Wang
d Faculty of Pharmacy and Pharmaceutical Sciences , Katz Group-Rexall Centre for Pharmacy & Health Research, University of Alberta , Edmonton , Alberta , Canada.
Reinhard
R
Vehring
d Faculty of Pharmacy and Pharmaceutical Sciences , Katz Group-Rexall Centre for Pharmacy & Health Research, University of Alberta , Edmonton , Alberta , Canada.
Raimar
R
Löbenberg
a Faculty of Pharmaceutical Sciences , University of São Paulo , São Paulo , São Paulo , Brazil.
Nádia Araci
NA
Bou-Chacra
D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D005665:Furosemide / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D012399:Rotation; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods
D014867:Water; D005665:Furosemide
Dissolution rate; drug delivery systems; high-energy milling; nanocrystals; poorly water-soluble drug