Data Article
Crystal structure analysis and fragmentation profile of lorcaserin hydrochloride hemihydrate

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Abstract

Lorcaserin, a 2,3,4,5-tetrahydro-3-benzazepine possessing a methyl and chloro groups in C-4 and C-9, respectively, is a drug currently used to treat obesity. Considering the role of the crystalline state to the understanding of the drug properties, allied to inexistence of solid state structural data in the worldwide accessible literature and database such as Crystallographic Cambridge Data Centre (CCDC), here we report the crystal structure of lorcaserin hydrochloride hemihydrate, inspecting in full detail its intra and intermolecular features for the first time, together with NMR data and fragmentation profile by ESI(+)-MS/MS.

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Rationale

Active pharmaceutical ingredients (APIs) in solid form possess a wide range of properties that have great impact in their physicochemical behavior [1]. Crystal solvates, salt formation and even packing modes can hugely influence the thermal stability, solubility, photo stability, and mechanical properties [2]. Therefore, the solid-state drugs studies could be essential to improve security and the choice criteria to select the best candidates for the marketing [3].

Lorcaserin (Scheme 1), a

Crystal preparation

Crystals were obtained from a dichloromethane saturated solution of lorcaserin hydrochloride using headspace vials perforated by a needle in order to occur slow evaporation. Crystals suitable for the single-crystal X-ray diffraction experiment were obtained after 3 weeks.

Single-crystal X-ray diffraction structure determination

Room temperature MoKα intensity data were acquired on a Bruker-AXS Kappa Duo diffractometer with an APEX II CCD detector. The structure was solved with SHELXS and refined with SHELXL-2018 [8]. Isotropic thermal parameters were

Structure description

Lorcaserin hydrochloride hemihydrate has crystallized in the orthorhombic space group P212121 with its asymmetric unit made up of two protonated drug molecules, two chloride anions and one water (Fig. 1). Besides the space group symmetry, the unit cell dimensions and content determined here (Table 1) were matched to those reported in a Chinese patent for the commercial crystal form of the drug [6], namely, orthorhombic space group P212121, a = 8.2396(4) Å, b = 11.5169(7) Å, c = 26.5462(13) Å,

Conclusion

In summary, we here described in full detail the conformational and packing aspects of the commercial crystal form of the anti-obesity drug lorcaserin using the single-crystal X-ray diffraction technique, together with its fragmentation profile by mass spectrometry. The structural data of its hydrochloride salt hemihydrate is now widely available for API quality control purposes, besides providing molecular information to rationalize its pharmaceutical performance and to design new crystal

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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