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

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.

Highlights

• Lamotrigine-nicotinamide cocrystals considerably increased solubility of the drug.

• Blending the cocrystal with polymers can extend its supersaturated state.

• Mixing the cocrystal with polymer powder increased Lamotrigine dissolution.

• Cellulose polymers prolonged the supersaturated state generated by the cocrystal.

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.

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Additional excipients in the paper: Kollicoat^® Smartseal 30 D, Sodium starch glycolate,

Isabela Fanelli Barreto Biscaia, Jaine Paula da Luz, Gabriel de Oliveira Hykavei, Larissa Sakis Bernardi, Paulo Renato de Oliveira, Polymer selection to increase in vitro supersaturation generated by lamotrigine nicotinamide monohydrate cocrystal: An evaluation with predissolved and solid polymers, Journal of Drug Delivery Science and Technology, Volume 73, 2022, 103451, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2022.103451.