Enhanced dissolution rate of simvastatin using spherical crystallization technique.
Simvastatin is a hypocholestrolemic drug that is insoluble in water. Its low water solubility rate limits the pharmacological effects. The aim of this study was to improve the dissolution rate of simvastatin using spherical crystallization method. The drug was dissolved in boiling dichloromethane as the good solvent. This solution was added to 5°C water as the non-solvent. After sedimentation, isopropyl acetate was added as the bridging solvent. At the end the crystals were collected and dried for 12 h in a 50°C oven. The FTIR and DSC results showed no change in the drug after crystallization process. XRPD studies showed the sharp peaks are present in the diffractograms of spherical crystals with minor reduction in height of the peaks. The particle size of spherical aggregates was about 37 μm and the dissolution efficiency of simvastatin up to 60 min increased to about 2-fold in phosphate buffer solution containing 0.5% sodium dodecyl sulfate (pH 7) using the rotating paddle method. Spherical crystals showed enhanced solubility than untreated powder possibly due to partial conversion to amorphous form. Their dissolution rate at 60 min was still 4-fold of untreated powder when stored at 25°C and 84% relative humidity for one month.
Varshosaz
Jaleh
J
Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. varshosaz@pharm.mui.ac.ir
Tavakoli
Naser
N
Salamat
Fatemeh Akhavan
FA
D000924:Anticholesteremic Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization / Q000379:methods*; D004058:Diffusion; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders / Q000737:chemistry; D019821:Simvastatin / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D014961:X-Ray Diffraction
D000924:Anticholesteremic Agents; D011208:Powders; D012997:Solvents; D019821:Simvastatin