Polymer selection to increase in vitro supersaturation generated by lamotrigine nicotinamide monohydrate cocrystal: An evaluation with predissolved and solid polymers

Abstract

Cocrystals can improve drug dissolution by generating supersaturated drug delivery systems. However, supersaturation is a high-energetic state with a tendency to precipitate. Polymers are used as precipitation inhibitors to inhibit nucleation or crystal growth. Our aim was to evaluate the influence of different polymers, predissolved or in powder form, on the supersaturation dissolution of lamotrigine-nicotinamide monohydrate (LAM.NIC.H2O) cocrystals. First, the polymers were dissolved in water. Hydroxypropyl methylcellulose polymers (HPMC E6 and HPMC K100LV) presented the greatest dissolution advantage, while polyvinylpyrrolidone presented the most stable dissolution profile. Then, the cocrystal and polymer powder mixture, in different proportions, were simultaneously added to water for dissolution and evaluated to identify the ideal cocrystal/polymer ratio for the development of a solid pharmaceutical dosage form. The cocrystal and polymer powder mixture of HPMC E6 and HPMC K100 LV (1:0.1 and 1:0.25, w/w) presented the best supersaturation enhancement with high area under the curve values. The study of FaSSIF for cocrystal and HPMC E6 powder mixture (1:0.1 and 1:0.25, w/w) presented promising results, as the supersaturated state was maintained for a relevant period. Thus, this study suggests a polymer selection design for supersaturation studies and supports the future development of LAM.NIC.H2O cocrystal solid formulations.