MOLECULAR COMPLEXES OF AGOMELATINE-PHOSPHORIC ACID: CRYSTAL
STRUCTURE DETERMINATION AND PHASE TRANSFORMATION KINETICS BY
NON-AMBIENT POWDER XRD
Raja Sekhar Voguri, Rama Reddy Chirla, and Archan Dey*
Address: Advanced Characterization Technology Lab, IPDO, Dr.Reddy’s Laboratories,
Hyderabad, India (e-mail: [email protected])
Co-crystals have been an alternative to polymorphs for the pharmaceutical industries to improve
active pharmaceutical ingredient’s (API) physicochemical properties and also commercial
advantages in intellectual property1. Molecular complex of agomelatine and phosphoric acid
(AGL-PA) was studied in this context. Possibility of salt formation of AGL-PA is low as being
with weakly ionizable amide functionality. Therefore agomelatine molecule is more prone to
form cocrystal2. Preliminary thermal studies revealed the solid-to-solid state phase
transformation of AGL-PA3. To investigate the transformation kinetics, non-ambient powderXRD was employed. Crystal structures4 determined from powder-XRD data revealed the
molecular level understating of the transformation5. This understanding is further evaluated from
solubility studies5.
1. Guidance for Industry: Regulatory Classification of Pharmaceutical Co-crystals.
Administration, FDA, Ed. Silver Spring: 2011.
2. Perumalla, S. R.; Sun, C. C., Synthon preference in O-protonated amide crystals - dominance
of short strong hydrogen bonds. CrystEngComm 2013, 15, 8941.
3. Kumar, V. S. R.; Krishna, B. V.; Charyulu, K. S.; Praveen, C.; Reddy, Y. S.; Dey, A.
Cocrystal of agomelatine with phosphoric acid. 2014, EP2743255A1.
4. Material Studio, Reflux, 7.0; Accelrys Software Inc.: San Diego, 2013.
5. Yan, Y.; Chen, J.-M.; Geng, N.; Lu, T.-B., Improving the Solubility of Agomelatine via
Cocrystals. Crystal Growth & Design 2012, 12, 2226.