Biomedical subjects

Marek Zakrzewski

Publications and source records attributed to Marek Zakrzewski.

3 recordsLinked to original sources

PubMed2004

Rationalizing the structural properties of bupivacaine base--a local anesthetic--directly from powder X-ray diffraction data.

Bupivacaine belongs to a family of 1-alkyl-2',6'-pipecoloxylidides, which has shown promise as reversible action potential blockers that can introduce prolonged local anesthetic effects. The crystal structure of the free-base form of bupivacaine has been determined directly from powder X-ray diffraction data using the Genetic Algorithm technique for structure solution, followed by Rietveld refinement. This work further emphasizes the scope and utility of ab initio structure solution directly from powder X-ray diffraction data for tackling structural problems within the biomedical field, leading to opportunities for the investigation of structure-property relationships.

Anesthetics, Local↗

PubMed2003

Polymorphism of a novel sodium ion channel blocker.

2-[[4-(4-Fluorophenoxy)phenyl]-methylene]-hydrazinecarboxamide, a member of the semicarbazone family which has shown potential therapeutic use as anticonvulsants, has been found to exist in two polymorphic forms denoted A and B. In addition to reporting aspects of the physical characterization of both forms, the crystal structure of polymorph A has been determined directly from powder X-ray diffraction data using the Genetic Algorithm technique for structure solution, followed by Rietveld refinement. This structure is compared with that of polymorph B, which was determined previously from single crystal X-ray diffraction data. Knowledge of the crystal structures of the two polymorphs provides the opportunity for establishing structure-property relationships. This work further emphasizes the scope and utility of ab initio structure solution from powder X-ray diffraction data in the pharmaceuticals field.

Calorimetry, Differential Scanning↗

PubMed2002

Investigation of solid-state reactions using variable temperature X-ray powder diffractometry. II. Aminophylline monohydrate.

PURPOSE: The object of this investigation was to demonstrate the utility of X-ray powder diffractometry (XRD) to study the kinetics of a complex pharmaceutical solid-state reaction wherein the reactant, product and intermediate phases were all simultaneously quantified. METHODS: Aminophylline monohydrate (I) decomposed to anhydrous theophylline (III) either directly or through an intermediate (anhydrous aminophylline, II). The reaction kinetics were studied isothermally at several temperatures ranging from 65 to 100 degrees C. By measuring the intensities of the XRD peaks unique to I, II and III, it was possible to simultaneously quantify the 3 phases during the entire reaction. RESULTS: Assuming that all the reaction steps follow first-order kinetics. the three equations describing the concentrations of I, II and III as a function of time, were derived. By fitting the experimental data to these equations, it was possible to obtain the rate constants for the three reaction steps. The rate constants were obtained at different temperatures and were used to draw Arrhenius type plots from which the activation energies were determined. At lower temperatures (< 80 degrees C). the concentration of the intermediate phase, i.e., II, was low throughout the reaction while at higher temperatures (> 90 degrees C), there was rapid formation and accumulation of II during the early stages of the reaction. These differences could be attributed to the fact that k1 (I --> II) had a more pronounced temperature dependence than k2 (I --> III) and k3 (II --> II). The XRD results were confirmed with isothermal thermogravimetry. CONCLUSIONS: Variable temperature XRD is a powerful tool to probe reaction kinetics in crystalline pharmaceuticals since it permits simultaneous quantification of multiple solid phases.

Aminophylline↗