Padrela, Luis and Rodrigues, Miguel A. and Velaga, Sitaram P. and Matos, Henrique A. and de Azevedo, Edmundo Gomes (2009) Formation of indomethacin-saccharin cocrystals using supercritical fluid technology. European Journal of Pharmaceutical Sciences, 38 (1). pp. 9-17.
Full text is not hosted in this archive but may be available via the Official URL, or by requesting a copy from the corresponding author.
Official URL: http://www.sciencedirect.com/science/article/B6T25...
The main objective of the present work is to check the feasibility of supercritical fluid (SCF) technologies in the screening and design of cocrystals (novel crystalline solids). The cocrystal formation tendencies in three different SCF techniques, focusing on distinct supercritical fluid properties – solvent, anti-solvent and atomization enhancer – were investigated. The effect of processing parameters on the cocrystal formation behaviour and particle properties in these techniques was also studied. A recently reported indomethacin–saccharin (IND–SAC) cocrystalline system was our model system. A 1:1 molar ratio of indomethacin (γ-form) and saccharin was used as a starting material. The SCF techniques employed in the study include the CSS technique (cocrystallization with supercritical solvent), the SAS technique (supercritical anti-solvent), and the AAS technique (atomization and anti-solvent). The resulting cocrystalline phase was identified using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform-Raman (FT-Raman). The particle morphologies and size distributions were determined using scanning electron microscopy (SEM) and aerosizer, respectively. The pure IND–SAC cocrystals were obtained from SAS and AAS processes, whilst partial to no cocrystal formation occurred in the CSS process. However, no remarkable differences were observed in terms of cocrystal formation at different processing conditions in SAS and AAS processes. Particles from CSS processes were agglomerated and large, whilst needle-to-block-shaped and spherical particles were obtained from SAS and AAS processes, respectively. The particle size distribution of these particles was 0.2–5 μm. Particulate IND–SAC cocrystals with different morphologies and sizes (nano-to-micron) were produced using supercritical fluid techniques. This work demonstrates the potential of SCF technologies as screening methods for cocrystals with possibilities for particle engineering.
|Uncontrolled Keywords:||Crystal engineering; Supercritical fluids; Indomethacin; Saccharin; Pharmaceutical cocrystals; Solid form screening|
|Subjects:||Biomedical Science > Nanomedicine|
|Deposited On:||04 Aug 2009 11:08|
|Last Modified:||04 Aug 2009 11:08|
Repository Staff Only: item control page