Formation and characterization of mefenamic acid-nicotinamide cocrystal during co-milling based on X-ray powder diffraction analysis

Abstract

Mefenamic acid (MFA) and Nicotinamide (NIC) cocrystal formation in co-milling treatment was investigated by x-ray powder diffractometry (XRPD). Two polymorphic form of Mefenamic acid (MFA form I and MFA form II) were used to form a cocrystal with nicotinamide. Co-milling treatment was carried out at room temperature in a 1: 2 molar ratio of MFA and NIC for various times up to 60 min. Samples were analyzed by XRPD. The XRPD showed that MFA form I and MFA form II formed cocrystal with NIC in the same diffractograms pattern. There was no intermediate amorphous form during milling process. The cocrystal formation mechanism was predicted via intermediate eutectic mixtures. The cocrystal formation from MFA form II (15 min) was faster than from MFA form I (45 min) which may explained by variations unit cell dimensions of MFA form I and MFA form II and also the polymorphic transformation of MFA form I.