Acta Pharm. 59 (2009) 245-257
Original research paper
Characterization of solvatomorphs of
methotrexate using thermoanalytical and other techniques
RENU
CHADHA, POONAM ARORA, RUPINDER KAUR, ANUPAM SAINI, MADAN LAL SINGLA and
DHARAMVIR SINGH JAIN
1 University
Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India
2 Central Scientific Instruments Organization,
Sector-30/C, Chandigarh-16003, India
3 Department
of Chemistry, Panjab University, Chandigarh-160014, India
Accepted July 6, 2009
Identification and characterization
of different forms of methotrexate were carried out by crystallization from
different solvents. Five different forms of the drug were obtained. Appearance
of a desolvation endotherm in the DSC accompanied by mass loss in TGA for forms
I, II, IV and V showed these forms to be acetonitrile solvate hydrate (form I),
trihydrate (forms II and IV) and dimethylformamide solvate (form V),
respectively. However, the desolvation peak was absent in form III (obtained
from methanol) indicating the absence of any solvent of crystallization. This
form was found to be partially crystalline by its XRPD pattern. Solution
calorimetry was further used to differentiate between the forms as they differ
in lattice energy, resulting in different enthalpies of solution. The
dissolution and solubility profiles were correlated with the enthalpy of
solution and subsequently with crystallinity of all the forms; the least
endothermic form (form III) had the highest dissolution rate.
Keywords: solvatomorph, pseudopolymorph, methotrexate, enthalpy of
solution, solution calorimetry, desolvation, dissolution rate