title: Dissolution enhancement of gliclazide using ultrasound waves and stabilizers in liquid anti-solvent precipitation.
abstract: The absorption rate of gliclazide is slow and variable among subjects probably due to poor dissolution from the dosage form. The objective of this study was to enhance the dissolution rate of gliclazide by reducing the particle size. Gliclazide was precipitated from an acetone solution by adding an antisolvent (water) containing stabilizers. A combination of jets (flow rate of 20 ml/min), ultrasound, HPMC 4000, and sodium dodecyl sulfate was used to control particle size and particle size distribution. The effects of concentration of stabilizers, initial drug concentration in solution, time of insonation, antisolvent-to-solvent ratio, and ultrasound power on particle size and particle size distribution were studied. Precipitated drug particles were characterized by laser diffraction particle size analysis, SEM, FTIR spectroscopy, DSC, powder x-ray diffraction and in-vitro dissolution. With increasing almost all the studied parameters, the particle size of gliclazide initially decreased, exhibited a minimum, and then increased. Drug particles of glicazide with a mean particle size of 1.56 ± 0.09 μm and a narrow size distribution (d10/d50/d90 = 0.67/1.67/2.26) were precipitated as compared to unprocessed gliclazide with a mean particle size of 10.67 ± 0.04 μm and a wide size distribution (d10/ds50/d90 = 4.53/9.88/18.03). SEM images indicated changes in the particle morphology. Powder x-ray diffraction patterns and DSC curves indicated no changes in the chemical properties but only decrease in crystallinity and/or particle size. The dissolution rate was enhanced 2.55-fold. In conclusion, drug particles with small size and narrow size distribution were precipitated by selecting favorable process conditions, and dissolution was enhanced several folds.
authors.forename: S S
authors.initials: SS
authors.lastname: Al-Nimry
authors.forename: A M
authors.initials: AM
authors.lastname: Qandil
authors.forename: M S
authors.initials: MS
authors.lastname: Salem
mesh_terms: D005079:Excipients; D005907:Gliclazide / Q000737:chemistry* / Q000528:radiation effects*; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000528:radiation effects*; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D012995:Solubility; D012997:Solvents; D014465:Ultrasonics
chemical_list: D005079:Excipients; D007004:Hypoglycemic Agents; D012997:Solvents; D005907:Gliclazide