TY - JOUR
T1 - Mechanistic Insight into Caffeine-Oxalic Cocrystal Dissociation in Formulations
T2 - Role of Excipients
AU - Duggirala, Naga Kiran
AU - Vyas, Amber
AU - Krzyzaniak, Joseph F.
AU - Arora, Kapildev K.
AU - Suryanarayanan, Raj
PY - 2017/11/6
Y1 - 2017/11/6
N2 - Caffeine-oxalic acid cocrystal, widely reported to be stable under high humidity, dissociated in the presence of numerous pharmaceutical excipients. In cocrystal-excipient binary systems, the water mediated dissociation reaction occurred under pharmaceutically relevant storage conditions. Powder X-ray diffractometry was used to identify the dissociated products obtained as a consequence of coformer-excipient interaction. The proposed cocrystal dissociation mechanism involved water sorption, dissolution of cocrystal and excipient in the sorbed water, proton transfer from oxalic acid to the excipient, and formation of metal salts and caffeine hydrate. In compressed tablets with magnesium stearate, the cocrystal dissociation was readily discerned from the appearance of peaks attributable to caffeine hydrate and stearic acid. Neutral excipients provide an avenue to circumvent the risk of water mediated cocrystal dissociation.
AB - Caffeine-oxalic acid cocrystal, widely reported to be stable under high humidity, dissociated in the presence of numerous pharmaceutical excipients. In cocrystal-excipient binary systems, the water mediated dissociation reaction occurred under pharmaceutically relevant storage conditions. Powder X-ray diffractometry was used to identify the dissociated products obtained as a consequence of coformer-excipient interaction. The proposed cocrystal dissociation mechanism involved water sorption, dissolution of cocrystal and excipient in the sorbed water, proton transfer from oxalic acid to the excipient, and formation of metal salts and caffeine hydrate. In compressed tablets with magnesium stearate, the cocrystal dissociation was readily discerned from the appearance of peaks attributable to caffeine hydrate and stearic acid. Neutral excipients provide an avenue to circumvent the risk of water mediated cocrystal dissociation.
KW - dissociation
KW - excipients
KW - formulations
KW - pharmaceutical cocrystals
KW - powder X-ray diffractometry
UR - http://www.scopus.com/inward/record.url?scp=85033405198&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85033405198&partnerID=8YFLogxK
U2 - 10.1021/acs.molpharmaceut.7b00587
DO - 10.1021/acs.molpharmaceut.7b00587
M3 - Article
C2 - 28990387
AN - SCOPUS:85033405198
VL - 14
SP - 3879
EP - 3887
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
SN - 1543-8384
IS - 11
ER -