Data ArticleCrystal structure analysis and fragmentation profile of lorcaserin hydrochloride hemihydrate
Graphical abstract
Section snippets
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.
References (12)
- et al.
Multicomponent Crystal of mefenamic acid and N-methyl-D-glucamine: crystal structures and dissolution study
J. Pharm. Sci.
(2019) - et al.
Pharmaceutical cocrystals, salts and multicomponent systems; intermolecular interactions and property based design
Adv. Drug Deliv. Rev.
(2017) - et al.
First identification and quantification of lorcaserin in an herbal slimming dietary supplement
J. Pharm. Biomed. Anal.
(2014) - et al.
Ionized form of acetaminophen with improved compaction properties
CrystEngComm
(2012) - Z.J. Shao, A.C. Blackburn, A.J. Grottick, M. Morgan, J.K. Rueter, A. Shifrina, S. Stirn, L. Yang, W.H. Yoon....
- S. Liu, G. Zhang, J. Gu, Preparation of large particles of monocrystalline lorcaserin hydrochloride, involves...