Amelioration of physicochemical, pharmaceutical, and pharmacokinetic properties of lornoxicam by cocrystallization with a novel coformer.

Objective: The present study was aimed to prepare and characterize new cocrystals of lornoxicam (LORX), a BCS class II drug employing 1,3-dimethyl urea (DMU) as a coformer to improve physicochemical, pharmaceutical, and pharmacokinetic performance.
Methods: A screening study was conducted by employing three techniques viz. neat grinding, liquid-assisted grinding (LAG), and solvent evaporation (SE) using different drug-coformer molar ratios (1:1, 1:2, and 1:3). Samples were characterized by DSC, PXRD, ATR-FTIR, SEM, intrinsic dissolution rate (IDR) studies, compressional studies, and pharmacokinetic studies. In vitro dissolution and stability studies (25 °C/60%RH and 40 °C/75%RH for three months) were carried out for cocrystal tablets.
Results: LAG and SE were found successful in ratio 1:3 and IDR showed approximately 28- and 19-fold increase, respectively in 0.1 N HCl (pH 1.2) and buffer (pH 7.4) as compared to pure LORX. The cocrystal exhibited good tabletability and was ∼2.5 times that of LORX at 6000 Psi. Dissolution profiles of tablets of cocrystal increased (56% and 100% at pH 1.2 and 7.4, respectively in contrast to those of physical mixture (PhyMix) (∼35% and ∼10%) and pure LORX (∼17% and ∼7%) within 60 min. The C _max and AUC _0-∞ for the selected cocrystal were significantly increased ( p  < 0.05) which was 2.4 and 2.5 times, respectively, that of LORX in a single dose oral pharmacokinetic study executed in rabbits. Tablets of cocrystal were found stable at both conditions.
Conclusion: The study indicates that cocrystallization with DMU can concomitantly improve tabletability, dissolution rate, and in vivo performance of dissolution limited drug LORX.