**Mariya A. Kryukova, Alexander V. Sapegin, Alexander S. Novikov, Mikhail Krasavin and Daniil M. Ivanov \***

Institute of Chemistry, Saint Petersburg State University, Universitetskaya Nab. 7/9, 199034 Saint Petersburg, Russia; mary\_kryukova@mail.ru (M.A.K.); sapegin\_yar@mail.ru (A.V.S.); ja2-88@mail.ru (A.S.N.); krasavintm@gmail.com (M.K.)

**\*** Correspondence: st024644@student.spbu.ru

Received: 28 March 2020; Accepted: 2 May 2020; Published: 5 May 2020

**Abstract:** For an active pharmaceutical ingredient, it is important to stabilize its specific crystal polymorph. If the potential interconversion of various polymorphs is not carefully controlled, it may lead to deterioration of the drug's physicochemical profile and, ultimately, its therapeutic efficacy. The desired polymorph stabilization can be achieved via co-crystallization with appropriate crystallophoric excipients. In this work, we identified an opportunity for co-crystallization of anastrozole (**ASZ**), a well-known aromatase inhibitor useful in second-line therapy of estrogen-dependent breast cancer, with a classical XB donor, 1,2,4,5-tetrafluoro-3,6-diiodobenzene (**1,4-FIB**). In the X-ray structures of **ASZ**·1.5 (**1,4-FIB**) co-crystal, different non-covalent interactions involving hydrogen and halogen atoms were detected and studied by quantum chemical calculations and QTAIM analysis at the ωB97XD/DZP-DKH level of theory.

**Keywords:** anastrozole; non-covalent interactions; halogen bonding; lp-π interactions; DFT; QTAIM
