1. Crystal and particle engineering : pharmaceutical cocrystals through antisolvent and liquid-liquid phase separation technologies
- Author
-
Sajid, Muhammad A.
- Subjects
Liquid-Liquid Phase Separation (LLPS) ,Oiling out ,Demixing ,Amorphous stabilisation ,Cocrystallisation ,Crystal engineering - Abstract
The effects of polymer concentration and solvents on cocrystal morphology of low solubility drugs were investigated, both of which had an impact. The melting temperatures also decreased with increasing polymer concentration. Placing the binding agent, benzene, at different interfaces induced morphological changes, such as formation of porous cocrystals. Previously liquid-liquid phase separation (LLPS) has been reported as a hindrance in the crystallisation process impeding further development. A phase diagram was constructed, and different phases were categorised into 4 types. After separation of the highly concentrated amorphous Oil Phase II, it was prone to gradual crystallisation. Crystallisation took place over 30-60 minutes; this allowed the in-situ monitoring. A novel cocrystallisation technique was developed; from (LLPS). Cocrystals of indomethacin with saccharin and nicotinamide were obtained by mixing Oil Phase II with the coformers. In-situ monitoring by spectroscopic had gradual changes in spectra; characteristic peaks increased in height and area with the formation of crystals until the reaction was complete. With crystal formation, the XRD spectra gradually had a sharper baseline due to a decrease in the amorphous indomethacin. The photoluminescence (PL) spectra displayed several peaks coupling into one large hump together with increasing intensity as the sample crystallised. There was a shift in the peak absorbance of the pure drug crystals obtained from LLPS and the indomethacin:saccharin cocrystal obtained from LLPS. Amorphous stabilisation was achieved by mixing polymer (PVP) with Oil Phase II. There were no changes to the XRD diffractogram as the sample did not undergo crystallisation.
- Published
- 2019