Molecular Dynamics Simulations of the Mechanically Induced Crystallization of Carbamazepine’s Trigonal Polymorph, CBZ(II) | Sciact - CRIS-система Института катализа

Molecular Dynamics Simulations of the Mechanically Induced Crystallization of Carbamazepine’s Trigonal Polymorph, CBZ(II) Научная публикация

Журнал

Structural Chemistry
ISSN: 1040-0400 , E-ISSN: 1572-9001

Вых. Данные

Год: 2026, DOI: 10.1007/s11224-026-02731-7

Ключевые слова

Carbamazepine polymorphs · Trigonal form · Palmitic acid · Mechanically induced transformation · Nucleation · Templating · Molecular dynamics · PIXEL calculations · Energy frameworks

Авторы

Kioseoglou Joseph ^1,2 , Boldyreva Elena ^3,4 , Kachrimanis Kyriakos ^2,5

Организации

1	School of Physics, Faculty of Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
2	Center for Interdisciplinary Research & Innovation, Aristotle University of Thessaloniki, Thessaloniki, Greece
3	Sobolev Institute of Geology and Mineralogy SB RAS, pr. Koptyuga, 3, Novosibirsk 630090, Russia
4	Novosibirsk State University, ul. Pirogova, 2, Novosibirsk 630090, Russia
5	Laboratory of Pharmaceutical Technology, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece

The present study investigates the mechanism by which the thermodynamically stable form of carbamazepine, CBZ(III), transforms to the trigonal polymorph, CBZ(II), during ball milling in the presence of palmitic acid. Crystal-structure and lattice-energy analyses were performed, and molecular dynamics (MD) simulations provided insight into crystalsurface and molecular-level phenomena underpinning the phase transformation. The PIXEL formalism and the all-atom Coulomb–London–Pauli method reproduced the experimentally observed stability order between CBZ(III) and CBZ(II). MD indicates limited miscibility between CBZ and palmitic acid—both at crystal surfaces and in the melt. The transformation proceeds via surface fluidization of CBZ(III) and hydrophobic-interaction–driven aggregation of CBZ around palmitic-acid alkyl chains. MD of palmitic-acid inclusion in CBZ(II) channels, together with pore analyses, suggests that stable inclusion would require lattice dilation. Trajectory inspection further shows frequent guest–wall repulsive contacts that can expel palmitic acid from the voids. Further work is warranted to test whether the transformation mechanism proposed for the polymorphic transformation of CBZ(III)→CBZ(II) generalizes to other mechanically induced solid-state transformations.

Kioseoglou J. , Boldyreva E. , Kachrimanis K.
Molecular Dynamics Simulations of the Mechanically Induced Crystallization of Carbamazepine’s Trigonal Polymorph, CBZ(II)
Structural Chemistry. 2026. DOI: 10.1007/s11224-026-02731-7 WOS OpenAlex

Поступила в редакцию:	14 нояб. 2025 г.
Принята к публикации:	15 янв. 2026 г.
Опубликована online:	6 февр. 2026 г.

≡ Web of science:	WOS:001681814000001
≡ OpenAlex:	W7127896749

≡ OpenAlex

Сбор данных от 15.02.2026