TY - JOUR
T1 - Unintended water mediated cocrystal formation in carbamazepine and aspirin tablets
AU - Arora, Kapildev K.
AU - Tayade, Nitin G.
AU - Suryanarayanan, Raj
PY - 2011/6/6
Y1 - 2011/6/6
N2 - The water of crystallization released during dehydration of dibasic calcium phosphate dihydrate (DCPD) mediated the cocrystal formation between carbamazepine (CBZ) and nicotinamide (NMA) in intact tablets. The dehydration of DCPD, the disappearance of the reactants (CBZ and NMA) and the appearance of the product (CBZ-NMA cocrystal) were simultaneously monitored by quantitative powder X-ray diffractometry. In a second model system, the water of crystallization released by the dehydration of DCPD caused the chemical decomposition of aspirin. Salicylic acid, one of the decomposition products, reacted with CBZ to form CBZ-salicylic acid cocrystal in tablets. This is the first report of cocrystal formation in intact tablets, demonstrating water mediated noncovalent synthesis in a multicomponent matrix. While the potential implications of such transformations, on both the mechanical and biopharmaceutical properties, can be profound, their characterization, using conventional solution based analytical techniques, can be challenging.
AB - The water of crystallization released during dehydration of dibasic calcium phosphate dihydrate (DCPD) mediated the cocrystal formation between carbamazepine (CBZ) and nicotinamide (NMA) in intact tablets. The dehydration of DCPD, the disappearance of the reactants (CBZ and NMA) and the appearance of the product (CBZ-NMA cocrystal) were simultaneously monitored by quantitative powder X-ray diffractometry. In a second model system, the water of crystallization released by the dehydration of DCPD caused the chemical decomposition of aspirin. Salicylic acid, one of the decomposition products, reacted with CBZ to form CBZ-salicylic acid cocrystal in tablets. This is the first report of cocrystal formation in intact tablets, demonstrating water mediated noncovalent synthesis in a multicomponent matrix. While the potential implications of such transformations, on both the mechanical and biopharmaceutical properties, can be profound, their characterization, using conventional solution based analytical techniques, can be challenging.
KW - Cocrystal
KW - X-ray diffractometry
KW - crystal growth
KW - dibasic calcium phosphate dihydrate
KW - excipients
KW - hydrates
KW - phase transformations
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U2 - 10.1021/mp200043u
DO - 10.1021/mp200043u
M3 - Article
C2 - 21548636
AN - SCOPUS:79958294605
SN - 1543-8384
VL - 8
SP - 982
EP - 989
JO - Molecular pharmaceutics
JF - Molecular pharmaceutics
IS - 3
ER -