Bohumil Kratochvíl

Bio: Bohumil Kratochvíl is an academic researcher from Institute of Chemical Technology in Prague. The author has contributed to research in topics: Crystal structure & Powder diffraction. The author has an hindex of 14, co-authored 158 publications receiving 754 citations. Previous affiliations of Bohumil Kratochvíl include Charles University in Prague.

Simvastatin: structure solution of two new low-temperature phases from synchrotron powder diffraction and ss-NMR

Abstract: Simvastatin is a substance used for the treatment of hypercholesterolemia. In addition to the already known room temperature structure of simvastatin (Cejka et al. in Acta Cryst C59:o428, 2003) two new low-temperature polymorphs were found by X-ray powder diffraction with the phase transition at 261 and 223 K (later confirmed by DSC to be 272 and 232 K). The main differences among three polymorphs consist in the side-chains conformation only and the phase changes are fully reversible. The structures of the polymorphs were studied by the powder diffraction based on synchrotron radiation as well as by solid-state NMR spectroscopy.

Ivabradine Hydrochloride (S)-Mandelic Acid Co-Crystal: In Situ Preparation during Formulation

Abstract: The pharmaceutical salt ivabradine hydrochloride is indicated for the symptomatic treatment of chronic stable angina pectoris and chronic heart failure. It exhibits extensive polymorphism and co-crystallization, which could be a way to provide an alternative solid form. We conducted a co-crystal screen, from which two hits were identified: with (S)-mandelic and (R)-mandelic acid. Both structures were determined from single-crystal X-ray diffraction data as co-crystals. The co-crystals were further characterized by common solid-state techniques, such as X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), solid-state NMR, IR and Raman spectroscopy, and dynamic vapor sorption (DVS). The co-crystal with (S)-mandelic acid was selected for further development; its physical and chemical stability was compared with two different polymorphs of the hydrochloride salt. The co-crystal exhibited a similar stability with the polymorph used in the original drug product and was, therefore, selected for formulation into the drug product. During the pre-formulation experiments, the in situ formation of the co-crystal was achieved during the wet granulation process. The following formulation experiments showed no influence of in situ prepared co-crystal on the overall stability of the bulk, when compared with pre-prepared co-crystal formulation.

Comparison of Compression and Material Properties of Differently Shaped and Sized Paracetamols

Abstract: Paracetamol is well-known API (active pharmaceutical ingredient) for its bad flow and compression abilities. To improve the compressibility, a high amount of excipient is commonly mixed with paracetamol to create better compressible material. Conversely, we used modified crystallization procedures to prepare plate, irregular and spherical particles from original raw paracetamol to prepare directly compressible API. To expand our screening, several sizes of each shape were prepared and material properties analyzed, mainly the flow and compression abilities, and significant variation of the properties presented; from very poor properties of raw paracetamol to excellent properties of spherical crystals which exhibited ability to be directly compressed without excipient. The analysis also showed very small effect of the size modification on tablet compression and material behavior as the main contribution had the shape alteration and compression force.

Iron uptake system of some members of the genus tolypocladium: crystal structure of the ligand and its iron(III) complex

Abstract: A new type of fungal hydroxamic acid (1′S,2′R,4′S,6′R)-3-(2′,4′-dimethyl-6′-vinylcyclohexyl)-1,4-dihydroxy-2(1H)-pyridone (tolypocin, HL) has been isolated from the mycelium of the fungus Tolypocladium geodes. The acid (C15H21NO3) crystallized from methanol [monoclinic, space group P21, Z= 4, a= 12.28(1), b= 9.958(5), c= 12.737(4), A, β= 94.91(5)°]. The structure was solved by direct methods and refined to a final R value of 0.055 for 2393 unique observed reflections. The iron(III) trischelate complex of this ligand [FeL3] has been isolated from the mycelium of the fungus Tolypocladium terricola. Its methanol solvate (C45H60FeN3O9·2MeOH) was crystallized from methanol [orthorhombic, space group P212121, Z= 4, a= 20.27(3), b= 19.35(5), c= 13.43(4)A]. The structure was solved by direct methods and refined to a final R value of 0.062 for 5562 observed reflections. The absolute configuration of the complex as determined from CD spectra and anomalous X-ray dispersion has been shown to be Λ-cis both in solution and in the solid state.

Ergogaline, a new ergot alkaloid, produced by claviceps purpurea : isolation, identification, crystal structure and molecular conformation

Abstract: A new peptide ergot alkaloid containing L-homoisoleucine has been isolated from ergot sclerotia of the field-growing parasitic fungus Claviceps purpurea. The molecular and crystal structures have been studied by X-ray analysis [ergogaline monohydrate, monoclinic space group P21 with two molecules per unit cell of the dimensions a= 9.972(1), b= 10.902(1) and c= 14.761 (1)A, β= 94.05(1)°] and compared with the structures in solution as determined by 2D NMR spectroscopy.

Creating Cocrystals: A Review of Pharmaceutical Cocrystal Preparation Routes and Applications

Abstract: Originally discovered almost a century ago, cocrystals continue to gain interest in the modern day due to their ability to modify the physical properties of solid-state materials, particularly pharmaceuticals. Intensification of cocrystal research efforts has been accompanied by an expansion of the potential applications where cocrystals can offer a benefit. Where once solubility manipulation was seen as the primary driver for cocrystal formation, cocrystals have recently been shown to provide attractive options for taste masking, mechanical property improvement, and intellectual property generation and extension. Cocrystals are becoming a commercial reality with a number of cocrystal products currently on the market and more following in registration and clinical trial phases. Increased commercialization of cocrystals has in turn necessitated additional research on methods to make cocrystals, with particular emphasis placed on emerging technologies that can offer environmentally attractive and efficient ...