Development of a First-Order Derivative UV Spectrophotometric Method for the Assay and Solubility Evaluation of Lamotrigine and Nicotinamide Cocrystals

Pharmaceutical cocrystals are composed of a drug and a coformer and are currently gaining attention due to their possibility of improving drug solubility. Quantitative determination of cocrystals is usually carried out by liquid chromatography method, but an alternative for the same is derivative UV spectrophotometry. Cocrystals of lamotrigine (LAM) were formed with nicotinamide (NIC) in order to improve the solubility of LAM. The aim of this study was to develop and validate a simple, low-cost, environment friendly, first-order derivative spectrophotometric method for simultaneous determination of LAM and NIC in cocrystals. Determination of LAM and NIC was performed at 244.4 and 271.6 nm, respectively. The method was accurate with recovery values of 98.21-101.52%, and precise (relative standard deviation (RSD) < 1.88%). Robustness evaluated by Plackett-Burman design showed no significant influence of the factors (pH, scanning speed, and sonication time) on LAM and NIC assays. The developed method was compared with a high performance liquid chromatography (HPLC) method and applied to study the cocrystal stoichiometry and solubility. The results indicated a molar ratio of 1:1 and that the cocrystal is more soluble than the drug. This study demonstrated that the first-order derivative method is feasible for drug and coformer determination in cocrystals and is a suitable alternative to chromatographic methods.