Andrzej Miklaszewski

Nanoscale size effect in in situ titanium based composites with cell viability and cytocompatibility studies

Novel in situ Metal Matrix Nanocomposite (MMNC) materials based on titanium and boron, revealed their new properties in the nanoscale range. In situ nanocomposites, obtained through mechanical alloying and traditional powder metallurgy compaction and sintering, show obvious differences to their microstructural analogue. A unique microstructure connected with good mechanical properties reliant on the processing conditions favour the nanoscale range of results of the Ti-TiB in situ MMNC example. The data summarised in this work, support and extend the knowledge boundaries of the nanoscale size effect that influence not only the mechanical properties but also the studies on the cell viability and cytocompatibility. Prepared in the same bulk, in situ MMNC, based on titanium and boron, could be considered as a possible candidate for dental implants and other medical applications. The observed relations and research conclusions are transferable to the in situ MMNC material group. Aside from all the discussed relations, the increasing share of these composites in the ever-growing material markets, heavily depends on the attractiveness and a possible wider application of these composites as well as their operational simplicity presented in this work.

In vitro biocompatibility of titanium after plasma surface alloying with boron.

Recently, the effect of different sizes of precursor powders during surface plasma alloying modification on the properties of titanium surface was studied. In this work we show in vitro test results of the titanium (α-Ti) after plasma surface alloying with boron (B). Ti-B nanopowders with 2 and 10wt% B were deposited onto microcrystalline Ti substrate. The in vitro cytocompatibility of these biomaterials was evaluated and compared with a conventional microcrystalline Ti. During the studies, established cell line of human gingival fibroblasts and osteoblasts were cultured in the presence of tested materials, and its survival rate and proliferation activity were examined. For this purpose, MTT assay, flow cytometric and fluorescent microscopic evaluation were made. Biocompatibility tests carried out indicate that the Ti after plasma surface alloying with B could be a possible candidate for dental implants and other medicinal applications. Plasma alloying is a promising method for improving the properties of titanium, thus increasing the field of its applications.

Development of β Type Ti23Mo-45S5 Bioglass Nanocomposites for Dental Applications

Titanium β-type alloys attract attention as biomaterials for dental applications. The aim of this work was the synthesis of nanostructured β type Ti23Mo-x wt % 45S5 Bioglass (x = 0, 3 and 10) composites by mechanical alloying and powder metallurgy methods and their characterization. The crystallization of the amorphous material upon annealing led to the formation of a nanostructured β type Ti23Mo alloy with a grain size of approximately 40 nm. With the increase of the 45S5 Bioglass contents in Ti23Mo, nanocomposite increase of the α-phase is noticeable. The electrochemical treatment in phosphoric acid electrolyte resulted in a porous surface, followed by bioactive ceramic Ca-P deposition. Corrosion resistance potentiodynamic testing in Ringer solution at 37 °C showed a positive effect of porosity and Ca-P deposition on nanostructured Ti23Mo 3 wt % 45S5 Bioglass nanocomposite. The contact angles of glycerol on the nanostructured Ti23Mo alloy were determined and show visible decrease for bulk Ti23Mo 3 wt % 45S5 Bioglass and etched Ti23Mo 3 wt % 45S5 Bioglass nanocomposites. In vitro tests culture of normal human osteoblast cells showed very good cell proliferation, colonization, and multilayering. The present study demonstrated that porous Ti23Mo 3 wt % 45S5 Bioglass nanocomposite is a promising biomaterial for bone tissue engineering.

Wear Improvement of Pure Titanium Surface by TiB Precipitation after Plasma Alloying Process

Good mechanical properties with combination of biocompatibility and high corrosion resistance make titanium and its alloys desirable materials for medical applications. A big disadvantage of titanium connects with its poor wear characteristics, however in this work this property was modified by boride microplasma surface alloying. Plasma surface alloying gives a wide range of layer thickness, which is controlled by the amount of the placed powder and process parameters like gas flow, nozzle diameter and current. Formation of TiB phase precipitation was confirmed by XRD analysis. Additionally, the modified microstructure was observed by optical microscopy. The Vickers microhardness was significantly improved from 180HV for original titanium substrate to 900HV in obtained composite layer structure, with a smoth hardness reduction in the cross section profile. Strong heat penetration from microplasma melt-in technique, results in substrate dissolution with formation of stable composite Ti + TiB layer. The surface corrosion resistance in 0.9% NaCl solution was nearly the same as for pure titanium, showing stable behavior of created oxide layer, with no negative effect of dual phase microstructure. Wear resistance of received composite layer structures were significantly improved in comparison with initial titanium samples.

Solid-state stability studies of crystal form of tebipenem

Abstract The aim of this study was to determine the kinetic and thermodynamic parameters of tebipenem degradation in the solid state. The process was analyzed based on the results obtained by a high performance liquid chromatography (HPLC) method using ultraviolet diode-array detector (DAD)/electrospray ionization tandem mass spectrometry (Q-TOF-MS/MS), Fourier transform infrared spectroscopy (FT-IR) and Raman spectroscopic (RS) studies. In dry air, the degradation of tebipenem was a first-order reaction depending on the substrate concentration while at an increased relative air humidity tebipenem was degraded according to the kinetic model of autocatalysis. The thermodynamic parameters: energy of activation (Ea), enthalpy (ΔH≠a) and entropy (ΔS≠a) of tebipenem degradation were calculated. Following a spectroscopic analysis of degraded samples of tebipenem, a cleavage of the β-lactam bond was proposed as the main degradation pathway, next confirmation using HPLC-Q-TOF-MS/MS method.

The Analysis of the Physicochemical Properties of Benzocaine Polymorphs

The study was a pioneering attempt to assess the influence of the structural polymorphism (forms I, II, III) of benzocaine on its solubility, apparent solubility, and chemical stability, which are vital parameters for preformulation and formulation work. The impact of differences in the solubility of selected polymorphs of benzocaine on their permeability through artificial biological membranes (PAMPA system) was evaluated. The polymorphs of benzocaine were obtained by means of techniques commonly used for the preparation of various pharmaceutical dosage forms: ball milling, micro milling, and cryogenic grinding, which allowed for the appearance or preservation of form III, the initial conformation of benzocaine. Ball milling resulted in the conversion of form III to I, whereas micro milling yielded form II. As a result of cryogenic grinding, form III of benzocaine was preserved. The identification of all polymorphic forms of benzocaine was confirmed via X-ray powder diffraction (PXRD) supported by FT-IR spectroscopy coupled with density functional theory (DFT) calculations. The differences in solubility, dissolution, and permeability through artificial biological membranes resulting from the polymorphic forms of benzocaine were established by using chromatographic determinations. Accelerated stability tests indicated that all polymorphic forms were chemically stable at a required level.

The Radiostability of Meropenem Trihydrate in Solid State

The influence of ionising radiation on the physicochemical properties of meropenem trihydrate in solid state was studied for doses of e-beam radiation: 25 kGy and 400 kGy. In the first part of our studies, we evaluated the possibility of applying radiosterilization to obtain sterile meropenem. No changes for meropenem irradiated with a dose of 25 kGy, the dose required to attain sterility, was confirmed in the results of spectroscopic (FT-IR), thermal (DSC, TGA) and X-ray powder diffraction (XRPD) studies. The radiation dose of 25 kGy produces no more than about 1500 ppm of radical defects. The chromatographic studies of irradiated meropenem in solutions did not show any chemical degradation. Moreover, the antimicrobial activity of meropenem irradiated with the dose of 25 kGy was unchanged. Based on the received results, we can conclude that radiostelization is a promising, alternative method for obtaining sterile meropenem. In the second part of the research, meropenem was exposed to e-beam radiation at the 400 kGy dose rate. It was confirmed, that reducing of antimicrobial activity could be connected with the degradation of β-lactam ring and changes in the trans-hydroxyethyl group. Apart from chemical changes, changes in the physical stability of irradiated meropenem (400 kGy) was also observed.

Effects of inclusion of cetirizine hydrochloride in β-cyclodextrin

Following the preparation of inclusion complex of cetirizine (CTZ) and β-cyclodextrin (β-CD), the compound was investigated to assess the possibility of modifying the physicochemical properties (solubility, release, stability, permeability) of CTZ after complexation that are vital for subsequent formulation studies involving the said complex. Changes in FT-IR/Raman spectra, DSC thermograms and XRD diffractograms confirmed the formation of a CTZ–β-CD system. Hydrophilic interaction chromatography with a DAD detector was employed to determine alterations of the CTZ concentration during studies following complexation. An analysis of a phase-solubility diagram of cCTZ = fcβ-CD indicated a linear rise in the solubility of CTZ as the concentration of β-CD increased. The inclusion of CTZ in a system with β-CD significantly reduced the instability of CTZ in the presence of oxidizing factors. It was also found that regardless of the pH of the acceptor fluids used in the release studies an increase was observed in the concentration of CTZ in CD system compared to its free form. The ability to permeate artificial biological membranes manifested by CTZ after complexation was enhanced as well. In summary, CD has significant potential to mask the bitter taste of CTZ and to counter the instability induced by oxidizing factors.