Kornelia Lewandowska

β-Cyclodextrin complexation as an effective drug delivery system for meropenem.

Following the preparation of an inclusion complex of β-cyclodextrin and meropenem, methods based on FT-IR, Raman and DSC were used for its characterization. An analysis of changes in the stability of meropenem after complexation showed that the complex may serve as a valuable delivery system significantly contributing to enhanced meropenem stability in aqueous solutions and in the solid phase. Due to a sustained transfer of meropenem from the cavity of the cyclodextrin it was possible to maintain a constant desired meropenem concentration over a period of 20 h, as confirmed by a release study. An evaluation of microbial activity not only demonstrated that the bactericidal action of meropenem was not stopped as a result of complexation but even pointed to greater growth inhibition in certain clinically important strains. The fact that investigations of meropenem stability and microbial activity proposed the carbonyl groups as those domains of a meropenem molecule that are instrumental in the formation of a complex with β-cyclodextrin supports the findings of theoretical studies based on molecular modeling.

Solid-state stability study of meropenem – solutions based on spectrophotometric analysis

BackgroundB-Lactam antibiotics are still the most common group of chemotherapeutic drugs that are used in the treatment of bacterial infections. However, due to their chemical instability the potential to apply them as oral pharmacotherapeutics is often limited and so it is vital to employ suitable non-destructive analytical methods. Hence, in order to analyze such labile drugs as β-lactam analogs, the application of rapid and reliable analytical techniques which do not require transferring to solutions or using organic solvents, following the current green approach to pharmaceutical analysis, is necessary. The main objective of the present research was to develop analytical methods for the evaluation of changes in meropenem in the solid state during a stability study.ResultsThe UV, FT-IR and Raman spectra of meropenem were recorded during a solid-state stability study. The optimum molecular geometry, harmonic vibrational frequencies, infrared intensities and Raman scattering activities were calculated according to the density-functional theory (DFT/B3LYP method) with a 6-31G(d,p) basis set. As the differences between the observed and scaled wavenumber values were small, a detailed interpretation of the FT-IR and Raman spectra was possible for non-degraded and degraded samples of meropenem. The problem of the overlapping spectra of meropenem and ring-containing degradation products was solved by measuring changes in the values of the first-derivative amplitudes of the zero-order spectra of aqueous solutions of meropenem. Also, molecular electrostatic potential (MEP), front molecular orbitals (FMOs) and the gap potential between highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) were determined.ConclusionsBased on the findings of this work, it appears possible to use time-saving and reliable spectrophotometric analytical methods, supported by quantum-chemical calculations, for solid-state stability investigations of meropenem. The methods developed for this study may be considered a novel, green solution to pharmaceutical analysis of labile drugs – an alternative for the recommended chromatographic procedures.

Complex of Rutin with β-Cyclodextrin as Potential Delivery System

This study aimed to obtain and characterize an RU-β-CD complex in the context of investigating the possibility of changes in the solubility, stability, antioxidative and microbiological activity as well as permeability of complexated rutin as against its free form. The formation of the RU-β-CD complex via a co-grinding technique was confirmed by using DSC, SEM, FT-IR and Raman spectroscopy, and its geometry was assessed through molecular modeling. It was found that the stability and solubility of the so-obtained complex were greater compared to the free form; however, a slight decrease was observed inits antibacterial potency. An examination of changes in the EPR spectra of thecomplex excluded any reducing effect of complexation on the antioxidative activity of rutin. Considering the prospect of preformulation studies involving RU-β-CD complexes, of significance is also the observed possibility of prolongedly releasing rutin from the complex at a constant level over along period of 20 h, and the fact that twice as much complexated rutin was able topermeate compared to its free form.

Application of spectroscopic methods for identification (FT-IR, Raman spectroscopy) and determination (UV, EPR) of quercetin-3-O-rutinoside. Experimental and DFT based approach.

Vibrational (FT-IR, Raman) and electronic (UV, EPR) spectral measurements were performed for an analysis of rutin (quercetin-3-O-rutinoside) obtained from Rutaofficinalis. The identification of rutin was done with the use of FT-IR and Raman spectra. Those experimental spectra were determined with the support of theoretical calculations based on a DFT method with the B3LYP hybrid functional and 6-31G(d,p) basis set. The application of UV and EPR spectra was found to be a suitable analytical approach to the evaluation of changes in rutin exposed to certain physicochemical factors. Differences in absorbance observed in direct UV spectra were used to monitor changes in the concentration of rutin in degraded samples. Spectra of electron paramagnetic resonance allowed studying the process of free-radical quenching in rutin following its exposure to light. The molecular electrostatic potential (MEP) and frontier molecular orbitals (LUMO-HOMO) were also determined in order to predict structural changes and reactive sites in rutin.

The use of UV, FT-IR and Raman spectra for the identification of the newest penem analogs: Solutions based on mathematic procedure and the density functional theory

The application of ultraviolet, FT-IR and Raman spectra was proposed for identification studies of the newest penem analogs (doripenem, biapenem and faropenem). An identification of the newest penem analogs based on their separation from related substances was achieved after the application of first derivative of direct spectra in ultraviolet which permitted elimination of overlapping effects. A combination of experimental and theoretical studies was performed for analyzing the structure and vibrational spectra (FT-IR and Raman spectra) of doripenem, biapenem and faropenem. The calculations were conducted using the density functional theory with the B3LYP hybrid functional and 6-31G(d,p) basis set. The confirmation of the applicability of the DFT methodology for interpretation of vibrational IR and Raman spectra of the newest penem analogs contributed to determination of changes of vibrations in the area of the most labile bonds. By employing the theoretical approach it was possible to eliminate necessity of using reference standards which - considering the instability of penem analogs - require that correction coefficients are factored in.

Indium–chlorine and gallium–chlorine tetrasubstituted phthalocyanines in a bulk system, Langmuir monolayers and Langmuir–Blodgett nanolayers – Spectroscopic investigations

The paper deals with spectroscopic characterization of metallic phthalocyanines (Pcs) (indium and gallium) complexed with chlorine and substituted with four benzyloxyphenoxy peripheral groups in bulk systems, 2D Langmuir monolayers and Langmuir-Blodgett nanolayers. An influence of the molecular structure of dyes (the presence of metal and of substitutes attached to the phthalocyanine macroring) on the in situ measurements of light absorption is reported. Molecular arrangement of the phthalocyanine molecular skeleton in the Langmuir monolayers on water substrate and in the Langmuir-Blodgett nanolayers is evaluated. A comparison of the light absorption spectra of the phthalocyanine monolayers with the spectra of the dyes in solution supports the existence of dye aggregates in the monolayer. It was shown that the type of dye aggregates (oblique and H types) depends markedly on the dye molecular structures. The NIR-IR, IR reflection-absorption and Raman spectra are also monitored for Langmuir-Blodgett nanolayers in non-polarized and polarized light. It was shown that the dye molecules in the Langmuir-Blodgett layers are oriented nearly vertically with respect to a gold substrate.

Raman and infrared studies of molecular orientation in fullerene–thiophene films

The paper deals with spectral studies (IR absorption, IR reflection–absorption, Raman scattering, and electronic absorption) of Langmuir–Blodgett layers of selected fullerene–thiophene dyads; some information on preparation and properties of the layers are also given. The spectra were recorded with unpolarised and polarised light (p-polarisation and s-polarisation) to receive data on orientation of the dyads with respect to the solid substrate and on interaction of the dyads with gold substrates. The comparison of the dyad spectra suggests redistribution of charges in both moieties of the dyads after films deposition on the substrate. We have shown that the polarised reflection–absorption spectra of the thin films are strongly dependent on the light polarisation. From the analysis of the data on the basis of the results obtained from various spectral methods it was concluded that the Langmuir–Blodgett layers are ordered and some parts of the dyads are oriented.

Solid-state stability studies of faropenem based on chromatography, spectroscopy and theoretical analysis.

Abstract Aim: The purpose of this study was to investigate the stability of faropenem in solid state. Results: The kinetic and thermodynamic parameters of degradation of faropenem were studied using an RP-HPLC method while the changes of spectral properties were investigated using derivative UV and FT-IR. Quantum-chemical calculations, based on the density functional theory, were carried out to support the estimation of the intra-ring stresses of faropenem and for theoretical interpretation of the spectra. The degradation of faropenem was a first-order reaction depending on the substrate concentration at an increased relative humidity and in dry air. The dependence ln k = f(1/T) became the ln k = (2.03 ± 3.22) × 104–(9761 ± 3052)(1/T) in dry air and ln k = (1.25 ± 0.22) × 105–(9004 ± 3479)(1/T ) at 90.0% RH. The thermodynamic parameters Ea, ΔH≠a, and ΔS≠a of the degradation of faropenem were calculated. The dependence ln k = f(RH%) assumed the form ln k = (7.58 ± 1.88) × 10−2 (RH%) – (5.90 ± 3.90) × 10−8. Conclusions: Stability studies of faropenem showed that the fusion of β-lactam and thiazolidine rings reduces the intra-ring stress, leading to a lower susceptibility to degradation in dry air and at increased RH.

Radiation Sterilization of Anthracycline Antibiotics in Solid State

The impact of ionizing radiation generated by a beam of electrons of 25–400 kGy on the stability of such analogs of anthracycline antibiotics as daunorubicin (DAU), doxorubicin (DOX), and epidoxorubicin (EPI) was studied. Based on EPR results, it was established that unstable free radicals decay exponentially with the half-time of 4 days in DAU and DOX and 7 days in EPI after irradiation. Radiation-induced structural changes were analyzed with the use of spectrophotometric methods (UV-Vis and IR) and electron microscope imaging (SEM). A chromatographic method (HPLC-DAD) was applied to assess changes in the contents of the analogs in the presence of their impurities. The study showed that the structures of the analogs did not demonstrate any significant alterations at the end of the period necessary for the elimination of unstable free radicals. The separation of main substances and related substances (impurities and potential degradation products) allowed determining that no statistically significant changes in the content of particular active substances occurred and that their conversion due to the presence of free radicals resulting from exposure to an irradiation of 25 kGy (prescribed to ensure sterility) was not observed.

Molecular Photodiode and Two-channel Optoelectronic Demultiplexer based on the [60]Fullerene-porphyrin Tetrad

Corresponding author. Email: szacilow@agh.edu.pl; szacilow@chemia.uj.edu.plPhotoelectrodes containing Langmuir–Blodget layers of [60]fullerene-porphyrin tetrad behave like photodiodes. Uponexcitation within the whole absorption spectrum of the molecule they generate photocurrent, the direction of whichdependsontheconductingsubstratepotential.Atnegativepolarizationhighintensitycathodicphotocurrentareobserved,while at positive polarization much weaker anodic photocurrents are observed. The forward-bias to reverse-bias currentratio amounts 5:1. Therefore the [60]fullerene-porphyrin tetrad is closely related to semiconductors showing photo-electrochemicalphotocurrentswitchingeffectandisapromisingmaterialformolecularoptoelectronics.Itcanbeusedasasimple molecular photodiode. Assignment of logic values to polarization of the photoelectrode and to light andphotocurrent pulses results in a very efficient two-channel optoelectronic demultiplexer.Manuscript received: 29 January 2011.Manuscript accepted: 21 July 2011.Moleculescomprisedofanelectrondonorandelectronacceptorwithdelocalizedp-electrons,linkedwithanaliphaticbridge,areof potential interest for molecular and organic electronics.