Supercritical antisolvent precipitation of nimesulide: preliminary experiments

• Published in: Current drug delivery Vol. 4; no. 3; p. 241
• Main Authors: Moneghini, M, Perissutti, B, Vecchione, F, Kikic, I, Alessi, P, Cortesi, A, Princivalle, F
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01-07-2007
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - chemistry; Calorimetry, Differential Scanning; Chemical Phenomena; Chemical Precipitation; Chemistry, Physical; Crystallization; Drug Stability; Drug Storage; Microscopy, Electron, Scanning; Particle Size; Pressure; Solubility; Solvents; Sulfonamides - chemistry; Thermodynamics; X-Ray Diffraction
• ISSN: 1567-2018
• DOI: 10.2174/156720107781023901

The purpose of this preliminary study was to investigate the physico-chemical properties of nimesulide precipitated by continuous supercritical antisolvent (SAS) from different organic solvents like acetone, chloroform and dichloromethane at 40 degrees C and 80, 85 and 88 bar, respectively. Scanning electron microscopy, differential scanning calorimetry, X-Ray diffractometry and in vitro dissolution tests were employed to study how the technological process and the solvent nature would affect the final product. SAS-processed nimesulide particles showed dramatic morphological change in crystalline structure if compared to native nimesulide, resulting in needle and thin rods shaped crystals. The solid state analysis showed that using chloroform or dichloromethane as a solvent the drug solid state remained substantially unchanged, whilst if using acetone the applied method caused a transition from the starting form I to the meta-stable form II. So as to identify which process was responsible for this result, nimesulide was further precipitated from the same solvent by conventional evaporation method (RV-sample). On the basis of this comparison, the solvent was found to be responsible for the re-organization into the different polymorphic form and the potential of the SAS process to produce micronic needle shaped particles, with an enhanced dissolution rate if compared to the to the pure drug, was ascertained. Finally, the stability of the nimesulide form II, checked by DSC analysis, was ruled on over a period of 15 months.