title: Halogen bonding and pharmaceutical cocrystals: the case of a widely used preservative.
abstract: 3-Iodo-2-propynyl-N-butylcarbamate (IPBC) is an iodinated antimicrobial product used globally as a preservative, fungicide, and algaecide. IPBC is difficult to obtain in pure form as well as to handle in industrial products because it tends to be sticky and clumpy. Here, we describe the preparation of four pharmaceutical cocrystals involving IPBC. The obtained cocrystals have been characterized by X-ray diffraction, solution and solid-state NMR, IR, and DSC analyses. In all the described cases the halogen bond (XB) is the key interaction responsible for the self-assembly of the pharmaceutical cocrystals thanks to the involvement of the 1-iodoalkyne moiety of IPBC, which functions as a very reliable XB-donor, with both neutral and anionic XB-acceptors. Most of the obtained cocrystals have improved properties with respect to the source API, in terms, e.g., of thermal stability. The cocrystal involving the GRAS excipient CaCl2 has superior powder flow characteristics compared to the pure IPBC, representing a promising solution to the handling issues related to the manufacturing of products containing IPBC.
authors.affiliation: NFMLab, Department of Chemistry, Politecnico di Milano, Via L. Mancinelli 7, 20131 Milan, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Baldrighi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Cavallo
authors.forename: Michele R
authors.initials: MR
authors.lastname: Chierotti
authors.forename: Roberto
authors.initials: R
authors.lastname: Gobetto
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Metrangolo
authors.forename: Tullio
authors.initials: T
authors.lastname: Pilati
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Resnati
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Terraneo
mesh_terms: D002152:Calorimetry, Differential Scanning; D002219:Carbamates / Q000737:chemistry* / Q000302:isolation & purification; D003460:Crystallization; D018360:Crystallography, X-Ray; D006219:Halogens / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D033362:Powder Diffraction; D011310:Preservatives, Pharmaceutical / Q000737:chemistry* / Q000302:isolation & purification; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D002219:Carbamates; D006219:Halogens; D011310:Preservatives, Pharmaceutical; C106572:3-iodo-2-propynylbutylcarbamate