Incomplete cocrystalization of ibuprofen and nicotinamide and its interplay with formation of ibuprofen dimer and/or nicotinamide dimer: A thermodynamic analysis based on DFT data
| Autor: | Gavin Walker, Saeed Shirazian, Milad Asgarpour Khansary |
|---|---|
| Přispěvatelé: | ERC, SFI, EU |
| Rok vydání: | 2020 |
| Předmět: |
Niacinamide
Dimer Pharmaceutical Science Ibuprofen 02 engineering and technology 030226 pharmacology & pharmacy Cocrystal Excipients 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Computational chemistry Phase (matter) Molecule ibuprofen Phase diagram Nicotinamide Chemistry organic chemicals Solvation 021001 nanoscience & nanotechnology cocrystalization Thermodynamics Density functional theory 0210 nano-technology Crystallization |
| Zdroj: | International journal of pharmaceutics. 591 |
| ISSN: | 1873-3476 |
| Popis: | peer-reviewed The authors have made available all associated files at: https://sites.google.com/view/makhansary/downloads, using tag ID: 2020.CoCryM.Thermo as per (1) MSCA Open Data policy and (2) our transparency of research data. The full text of this article will not be available in ULIR until the embargo expires on the 20/10/2021 Cocrystallization of ibuprofen and nicotinamide in hot melt extrusion process has been subject of many studies addressing low ibuprofen bioavailability. However, it is observed that the process of cocrystal formation of ibuprofen and nicotinamide might be incomplete. We hypothesized that formation of dimers of ibuprofen–ibuprofen or dimers nicotinamide– nicotinamide might be the cause of such poor cocrystalization process by altering the phase behaviour of the mixture. This paper addresses the molecular thermodynamics of mixtures of ibuprofen and nicotinamide, with special focus on the possibility of formation of these dimers and their corresponding interplay with mixture phase behaviour. For this purpose, density functional theory calculations are used to calculate electron donor-acceptor sizes on each molecule and accordingly possible dimers of each molecule are analysed. The free energies and phase diagram are determined for (1) when a dimer is formed or (2) no dimer is formed, over a wide operating temperature range of 273.15 K–390 K. The binding and solvation energies are calculated to identify/rank dimers. Calculations showed that formation of dimers requires an energy input which can be accessible noting to the external heating in hot melt extrusion process. The calculated solvation energies of the dimers suggest that addition of liquid binder (water) can mitigate the risk of dimer formations. Addition of proper binder/excipient is an easy route to compensate such dimer formation and to engineer ibuprofen and nicotinamide cocrystallization behaviour. |
| Databáze: | OpenAIRE |
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