Jaan Aruväli

Towards improved solubility of poorly water-soluble drugs: cryogenic co-grinding of piroxicam with carrier polymers

Abstract Amorphous solid dispersions (SDs) open up exciting opportunities in formulating poorly water-soluble active pharmaceutical ingredients (APIs). In the present study, novel catalytic pretreated softwood cellulose (CPSC) and polyvinylpyrrolidone (PVP) were investigated as carrier polymers for preparing and stabilizing cryogenic co-ground SDs of poorly water-soluble piroxicam (PRX). CPSC was isolated from pine wood (Pinus sylvestris). Raman and Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used for characterizing the solid-state changes and drug–polymer interactions. High-resolution scanning electron microscope (SEM) was used to analyze the particle size and surface morphology of starting materials and final cryogenic co-ground SDs. In addition, the molecular aspects of drug–polymer interactions and stabilization mechanisms are presented. The results showed that the carrier polymer influenced both the degree of amorphization of PRX and stabilization against crystallization. The cryogenic co-ground SDs prepared from PVP showed an enhanced dissolution rate of PRX, while the corresponding SDs prepared from CPSC exhibited a clear sustained release behavior. In conclusion, cryogenic co-grinding provides a versatile method for preparing amorphous SDs of poorly water-soluble APIs. The solid-state stability and dissolution behavior of such co-ground SDs are to a great extent dependent on the carrier polymer used.

The electrochemical activity of two binary alloy catalysts toward oxygen reduction reaction in 0.1 M KOH

The platinum group metals (Pt, Ir and Ru) and the carbide-derived carbon support with the very high specific surface area were used to synthesise the low noble metal loading Pt-C, IrPt-C and RuPt-C alloy catalysts. The alloying of the platinum group metals in the studied catalysts was proved by the several independent physical characterization methods like: the X-ray diffraction, time of flight secondary ion mass-spectrometry, X-ray photoelectron spectroscopy, scanning and transmission electron microscopy. The electrocatalytic activity toward oxygen reduction reaction of the synthesised catalysts in an alkaline solution was studied and compared with the commercially available Pt-Vulcan. The combined and detail approach using the transmission electron microscopy and inductively coupled plasma mass spectrometry for estimation of the surface area of metal particles is provided. The noticeably higher calculated mass corrected and specific kinetic current density values for Pt-C catalyst were established. For IrPt-C and RuPt-C alloy catalysts, mass corrected current density values are comparable with the commercial Pt-Vulcan. The specific kinetic current density values increase in the following sequence: RuPt-C < IrPt-C < Pt-Vulcan < Pt-C.

Interactions between Chloramphenicol, Carrier Polymers, and Bacteria–Implications for Designing Electrospun Drug Delivery Systems Countering Wound Infection

Antibacterial drug-loaded electrospun nano- and microfibrous dressings are of major interest as novel topical drug delivery systems in wound care. In this study, chloramphenicol (CAM)-loaded polycaprolactone (PCL) and PCL/poly(ethylene oxide) (PEO) fiber mats were electrospun and characterized in terms of morphology, drug distribution, physicochemical properties, drug release, swelling, cytotoxicity, and antibacterial activity. Computational modeling together with physicochemical analysis helped to elucidate possible interactions between the drug and carrier polymers. Strong interactions between PCL and CAM together with hydrophobicity of the system resulted in much slower drug release compared to the hydrophilic ternary system of PCL/PEO/CAM. Cytotoxicity studies confirmed safety of the fiber mats to murine NIH 3T3 cells. Disc diffusion assay demonstrated that both fast and slow release fiber mats reached effective concentrations and had similar antibacterial activity. A biofilm formation assay revealed that both blank matrices are good substrates for the bacterial attachment and formation of biofilm. Importantly, prolonged release of CAM from drug-loaded fibers helps to avoid biofilm formation onto the dressing and hence avoids the treatment failure.

Suberin Fatty Acids from Outer Birch Bark: Isolation and Physical Material Characterization

The isolation and physical material properties of suberin fatty acids (SFAs) were investigated with special reference to their potential applications as novel pharmaceutical excipients. SFAs were isolated from outer birch bark (OBB) with a new extractive hydrolysis method. The present simplified isolation process resulted in a moderate batch yield and chemical purity of SFAs, but further development is needed for establishing batch-to-batch variation. Cryogenic milling was the method of choice for the particle size reduction of SFAs powder. The cryogenically milled SFAs powder exhibited a semicrystalline structure with apparent microcrystalline domains within an amorphous fatty acids matrix. The thermogravimetric analysis (TGA) of SFAs samples showed a good thermal stability up to 200 °C, followed by a progressive weight loss, reaching a plateau at about 95% volatilization at about 470 °C. The binary blends of SFAs and microcrystalline cellulose (MCC; Avicel PH 101) in a ratio of 25:75 (w/w) displayed good powder flow and tablet compression properties. The corresponding theophylline-containing tablets showed sustained or prolonged-release characteristics. The physicochemical and bulk powder properties of SFAs isolated from OBB are auspicious in terms of potential pharmaceutical excipient applications.

Influence of humidified synthetic air feeding conditions on the stoichiometry of (La1-xSrx)yCoO3−δ and La0.6Sr0.4Co0.2Fe0.8O3−δ cathodes under applied potential measured by electrochemical in situ high-temperature XRD method

The solid oxide fuel cell symmetrical cells with porous (La1-xSrx)yCoO3−δ and La0.6Sr0.4Co0.2Fe0.8O3−δ electrodes for intermediate temperature applications have been studied under electrochemical polarization and synthetic air + H2O vapor (so called moisturized cathode gas) feeding conditions using high-temperature electrochemical in situ X-ray diffraction method, chronoamperometry, cyclic voltammetry, and impedance spectroscopy methods. Changes in the lattice parameters and electrochemical activity of La0.6Sr0.4CoO3−δ, (La0.6Sr0.4)1.01CoO3−δ, (La0.6Sr0.4)0.99CoO3−δ and La0.6Sr0.4Co0.2Fe0.8O3−δ were calculated depending on the temperature (T), electrode potential (E), and oxygen partial pressure (pO2) applied. Influence of H2O vapor in synthetic air on (La1-xSrx)yCoO3−δ parameters was irreversible and continued expansion of (La1-xSrx)yCoO3−δ lattice observed in H2O vapor + synthetic air feeding conditions has been observed continuously after changing wet cathode gas to dry oxygen. Nearly, reversible behavior of La0.6Sr0.4Co0.2Fe0.8O3−δ lattice has been established and for La0.6Sr0.4Co0.2Fe0.8O3−δ, the cell volume and polarization resistance started to decrease after changing humidified synthetic air to dry synthetic air in the cathode compartment. For the slightly cationic deficient (La0.6Sr0.4)0.99CoO3−δ, the cathode structure is more stable and the electroreduction of the oxygen was faster. Detailed comparison of experimental data demonstrates that the dependence of the crystallographic parameters on the electrode potential and temperature applied is in a good agreement with the electrochemical impedance spectroscopy data, indicating that the electrocatalytic activity of the cathode decreases with the rise of Fe ion concentration in B-position of LSCF cathode.