Formation of Indomethacin-Saccharin Cocrystals during Wet Granulation: Role of Polymeric Excipients

Ryoma Tanaka; Naga Kiran Duggirala; Yusuke Hattori; Makoto Otsuka; Raj Suryanarayanan

doi:10.1021/acs.molpharmaceut.9b01004

Formation of Indomethacin-Saccharin Cocrystals during Wet Granulation: Role of Polymeric Excipients

Ryoma Tanaka, Naga Kiran Duggirala, Yusuke Hattori, Makoto Otsuka, Raj Suryanarayanan

Pharmaceutics

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	274-283
Number of pages	10
Journal	Molecular pharmaceutics
Volume	17
Issue number	1
DOIs	https://doi.org/10.1021/acs.molpharmaceut.9b01004
State	Published - Jan 6 2020

Bibliographical note

Funding 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.

Publisher Copyright:
© 2019 American Chemical Society.

Keywords

chemometrics
cocrystal
continuous processing
excipient
high-shear wet granulation
kinetics
polymer
poorly water-soluble drug

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

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title = "Formation of Indomethacin-Saccharin Cocrystals during Wet Granulation: Role of Polymeric Excipients",

abstract = "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.",

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Formation of Indomethacin-Saccharin Cocrystals during Wet Granulation: Role of Polymeric Excipients

Abstract

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Keywords

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