Formulation of a cocrystal into a solid pharmaceutical dosage form entails numerous processing steps during which there is risk of dissociation. In an effort to reduce the number of unit operations, we have attempted the in situ formation of an indomethacin-saccharin (INDSAC) cocrystal during high-shear wet granulation (HSWG). HSWG of IND (poorly water-soluble drug) and SAC (coformer), with polymers (granulating agents), was carried out using ethanol as the granulation liquid and yielded INDSAC cocrystal granules. Therefore, cocrystal formation and granulation were simultaneously accomplished. Our objectives were to (i) evaluate the influence of polymers on cocrystal formation kinetics during wet granulation and (ii) mechanistically understand the role of polymers in facilitating the cocrystal formation. Polyvinylpyrrolidone (PVP), hydroxypropyl cellulose (HPC), and polyethylene oxide (PEO) were chosen to investigate the influence of soluble polymers. The cocrystal formation kinetics was influenced by the polymer (PVP < HPC < PEO) and its concentration. The interaction of the polymer with cocrystal components inhibited the cocrystal formation. Complete cocrystal formation was observed in the presence of PEO, a polymer which does not interact with IND and SAC.
Bibliographical noteFunding Information:
We thank Drs. Kazuhide Ashizawa, Seema Thakral, Anasuya Sahoo, and Jinghan Li for their help. This research was supported by the William and Mildred Peters Endowment Fund, Grant-in-Aid for JSPS Fellows (grant number JP19J15135) and JSPS Overseas Challenge Program for Young Researchers. Parts of this work were carried out in the Characterization Facility and Minnesota Nano Center, University of Minnesota, which receives partial support from NSF through the MRSEC and NNCI program, respectively.
© 2019 American Chemical Society.
- continuous processing
- high-shear wet granulation
- poorly water-soluble drug
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't