Commonly applied approaches to enhance the dissolution properties of low water-soluble crystalline active pharmaceutical ingredients (APIs) include their amorphization by incorporation into a polymeric matrix and the formation of amorphous solid dispersions, or blending APIs with low-molecular-weight excipients and the formation of a co-amorphous system. This study focused on the preparation and characterization of binary (consisting of indomethacin (IND) and polymer - copovidone (PVP VA 64), as a carrier, or amino acid - L-arginine (ARG), as a co-former) and ternary (comprising the same API, polymer, and amino acid) formulations. Formulations were produced by ball milling (BM) and/or hot-melt extrusion (HME), and extensive physicochemical characterization was performed. Specifically, the physicochemical and solid-state properties of a model IND-ARG system incorporated into a polymeric matrix of PVP VA 64 by HME and BM as well as by combined BM/HME method together with the impact of the preparation strategy on the dissolution profiles and long-term physical stability were investigated. Ball-milled binary and ternary formulations were found to be amorphous. The residual crystals corresponding to IND-ARG salt were identified in the ternary formulations produced via HME. Despite the presence of a crystalline phase, dissolution tests showed that ternary systems prepared by HME exhibited improved IND solubility when compared to pure crystalline IND and their corresponding physical mixture. None of the binary and ternary formulations that were initially fully amorphous did undergo recrystallization during the entire period of preservation (minimum of 12 months) in dry conditions at 25 °C.

• MeSH
• arginin * MeSH
• indomethacin * MeSH
• polymery MeSH
• rozpustnost MeSH
• vinylové sloučeniny MeSH
• Publikační typ
• časopisecké články MeSH

Injectable depot formulations are aimed at providing long-term sustained release of a drug into systemic circulation, thus reducing plasma level fluctuations and improving patient compliance. The particle size distribution of the formulation in the form of suspension is a key parameter that controls the release rate. In this work, the process of wet stirred media milling (ball milling) of a poorly water-soluble substance has been investigated with two main aims: (i) to determine the parametric sensitivity of milling kinetics; and (ii) to develop scale-up methodology for process transfer from batch to flow-through arrangement. Ball milling experiments were performed in two types of ball mills, a batch mill with a 30ml maximum working volume, and a flow-through mill with a 250ml maximum working volume. Milling parameters were investigated in detail by methodologies of QbD to map the parametric space. Specifically, the effects of ball size, ball fill level, and rpm on the particle breakage kinetics were systematically investigated at both mills, with an additional parameter (flow-rate) in the case of the flow-through mill. The breakage rate was found to follow power-law kinetics with respect to dimensionless time, with an asymptotic d50 particle size in the range of 200-300nm. In the case of the flow-through mill, the number of theoretical passes through the mill was found to be an important scale-up parameter.

• MeSH
• farmaceutická chemie metody   MeSH
• injekce MeSH
• léky s prodlouženým účinkem aplikace a dávkování   chemická syntéza   MeSH
• nanočástice chemie   MeSH
• rozpustnost MeSH
• suspenze MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH

Meloxicam (MLX) is a poorly soluble drug exhibiting strong hydrophobicity. This combination of properties makes dissolution enhancement by particle size reduction ineffective; therefore, combined formulation approaches are required. Various approaches were investigated in this study, including milling, solid dispersions, and self-emulsified lipid formulations. Whereas milling studies of MLX and its co-milling with various polymers have been reported in recent literature, this study is focused on investigating the dissolution kinetics of particulate formulations obtained by co-milling MLX with sodium lauryl sulfate (SLS) in a planetary ball mill with 5-25 wt.% SLS content. The effects of milling time and milling ball size were also investigated. No significant reduction in drug crystallinity was observed under the investigated milling conditions according to XRD data. For the dissolution study, we used an open-loop USP4 dissolution apparatus, and recorded dissolution profiles were fitted according to the Weibull model. The Weibull parameters and a novel criterion-surface utilization factor-were used to evaluate and discuss the drug release from the perspective of drug particle surface changes throughout the dissolution process. The most effective co-milling results were achieved using smaller balls (2 mm), with a co-milling time of up to 15 min SLS content of up to 15 wt.% to increase the dissolution rate by approximately 100 times relative to the physical mixture reference. The results suggest that for hydrophobic drugs, particle performance during dissolution is very sensitive to surface properties and not only to particle size. Co-milling with SLS prepares the surface for faster drug release than that achieved with direct mixing.

• Publikační typ
• časopisecké články MeSH

Aim: Fabrication of nanopepper (NP) for antibacterial application and elucidation of its molecular and cellular biocompatibility. Materials & methods: Synthesis of NP was achieved using a high-energy ball milling method. Following characterization, its antibacterial activity and cellular and molecular biocompatibility were evaluated in vitro by experimental and computational approaches. Results: A total of 15 h of milling pepper produced NP with a size of 44 ± 12 nm and zeta potential of -22 ± 12 mV. Bulk pepper and NP showed antibacterial activity and an LC50 of 1.9 μM and 2.1 μM in HCT116 colon cells. Components of pepper, piperine and β-caryophyllene were found to interact with superoxide dismutase [Cu-Zn] and apoptotic protease-activating factor-1-caspase-9 through different amino acids via H-bonds. Conclusion: NP exhibits significant antibacterial activity with cellular biocompatibility due to intrinsic atomic interaction. Aim: Fabrication of nanopepper (NP) for antibacterial application and elucidation of its molecular and cellular biocompatibility. Materials & methods: Synthesis of NP was achieved using a high-energy ball milling method. Following characterization, its antibacterial activity and cellular and molecular biocompatibility were evaluated in vitro by experimental and computational approaches. Results: A total of 15 h of milling pepper produced NP with a size of 44 ± 12 nm and zeta potential of -22 ± 12 mV. Bulk pepper and NP showed antibacterial activity and an LC50 of 1.9 μM and 2.1 μM in HCT116 colon cells. Components of pepper, piperine and β-caryophyllene were found to interact with superoxide dismutase [Cu-Zn] and apoptotic protease-activating factor-1-caspase-9 through different amino acids via H-bonds. Conclusion: NP exhibits significant antibacterial activity with cellular biocompatibility due to intrinsic atomic interaction.

• MeSH
• antibakteriální látky farmakologie   MeSH
• antiinfekční látky * MeSH
• HCT116 buňky MeSH
• lidé MeSH
• Piper nigrum * MeSH
• superoxiddismutasa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

One of the conventional methods of alleviating the problem of poor drug solubility is the particle size reduction. The efficiency of this approach depends on successful formulation suppressing the drug agglomeration. The aim of this study was to circumvent the dissolution problems of model hydrophobic meloxicam drug (MLX) by using liquid media of different wetting capacity to comminute and formulate a rapidly dissolving carrier system without the use of surfactants. Micro-suspensions of MLX were prepared by ball milling, using water or n-Heptane as a liquid medium. The suspensions were used as granulation liquids to formulate granulate from microcrystalline cellulose and lactose mixture. The release kinetics from prepared granulates were studied using the USP-4 dissolution apparatus. Micro-suspensions prepared via wet milling in non-water liquid media exhibited a massive improvement of release rate compared with source meloxicam and they outperformed their water-milled counterparts. The release rates from those formulations, despite not comprising any surfactant, were comparable to those obtained by different authors using surfactant stabilized nanosuspension formulations. Thus, they can present an interesting formulation alternative for hydrophobic drugs that are dissolution limited.

• MeSH
• celulosa MeSH
• kinetika MeSH
• laktosa MeSH
• meloxikam aplikace a dávkování   chemie   MeSH
• nanostruktury MeSH
• nosiče léků chemie   MeSH
• povrchově aktivní látky MeSH
• rozpustnost MeSH
• suspenze MeSH
• uvolňování léčiv MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH

TiO2 is the most studied photocatalyst because of its non-toxicity, chemical stability, and low cost. However, the problem of TiO2 is its low activity in the visible region of the spectrum. In this study, we focused on the preparation of composite photocatalytic materials with altered light absorption properties. TiO2 P25 and various metal oxides were mechanically joined by ball-milling and immobilized on glass plates. The prepared samples were evaluated based on their ability to degrade NO in gas phase. The formation of undesirable byproducts was also investigated. Four best performing composites were later chosen, characterized, and further evaluated under various conditions. According to their performance, the metal oxide additives can be divided into three groups. P25/Fe2O3 showed the most promising results-an increase in overall deNOx activity under modified ISO conditions and altered selectivity (less NO2 is formed) under both simulated outdoor and simulated indoor conditions. On the other hand, P25/V2O5 composite showed negligible photocatalytic activity. The intermediate group includes P25/WO3 and P25/ZnO photocatalysts, whose performances are similar to those of pristine P25.

• MeSH
• katalýza MeSH
• oxidy * MeSH
• titan * chemie   MeSH
• Publikační typ
• časopisecké články MeSH

Po více než dvaceti letech opět vychází jedinečné dílo Jana Amose Komenského - ORBIS SENSUALIUM PICTUS (Svět v obrazech), které by nemělo chybět v žádné rodinné i školní knihovně. Jedná se o výbor z Komenského jazykové encyklopedie, která v době svého vydání natolik předběhla dobu, že ještě v následujících staletích - u nás až do počátku minulého století - sloužila jako živá učební pomůcka pro výuku jazyků. Aktuální vydání připravil kolektiv odborníků pod vedením doc. PhDr. Naděždy Kvítkové, CSc. a doplnil jej obsáhlým úvodem a komentářem k dílu. Nové vydání obsahuje původní latinské texty a je nově doplněno paralelními překlady do současné češtiny, němčiny, angličtiny a ruštiny. Neméně důležitou součástí knihy je i obrazová část, která reprodukuje původní dřevoryty z několika historických vydání a snaží se tak netradičním způsobem srovnat i vývoj obrazové kultury dané doby.; Po více než dvaceti letech opět vychází jedinečné dílo Jana Amose Komenského – ORBIS SENSUALIUM PICTUS (Svět v obrazech), které by nemělo chybět v žádné rodinné i školní knihovně. Jedná se o výbor z Komenského jazykové encyklopedie, která v době svého vydání natolik předběhla dobu, že ještě v následujících staletích – u nás až do počátku minulého století – sloužila jako živá učební pomůcka pro výuku jazyků. Aktuální vydání připravil kolektiv odborníků pod vedením doc. PhDr. Naděždy Kvítkové, CSc. a doplnil jej obsáhlým úvodem a komentářem k dílu. Nové vydání obsahuje původní latinské texty a je nově doplněno paralelními překlady do současné češtiny, němčiny, angličtiny a ruštiny. Neméně důležitou součástí knihy je i obrazová část, která reprodukuje původní dřevoryty z několika historických vydání a snaží se tak netradičním způsobem srovnat i vývoj obrazové kultury dané doby.

The polyaniline (PANI) base was ball-milled with silver nitrate in the solid state. Samples were prepared at various mole ratios of silver nitrate to PANI constitutional units ranging from 0 to 1.5 for three processing times, 0, 5, and 10 min. The emeraldine form of PANI was oxidized to pernigraniline, and the silver nitrate was reduced to metallic silver. Nitric acid is a byproduct, which may protonate the residual emeraldine and pernigraniline. The changes occurring in the structure of PANI are discussed on the basis of Fourier transform IR and Raman spectroscopies. Raman spectra revealed the formation of pernigraniline salt. The reaction between the two nonconducting components, emeraldine base and silver nitrate, produced a mixture of two conducting components, emeraldine or pernigraniline nitrate and metallic silver. The accompanying conductivity changes were determined. The increase in the conductivity of the original base, 10(-9) S cm(-1), up to 10(-2) S cm(-1) was found to depend on the mole ratio of silver nitrate to PANI base and on the processing time of the components in the ball mill.

• MeSH
• aniliny chemie   MeSH
• časové faktory MeSH
• chemické modely MeSH
• dusičnan stříbrný chemie   MeSH
• elektrická vodivost MeSH
• kyslík chemie   MeSH
• organická chemie metody   MeSH
• polymery chemie   MeSH
• Ramanova spektroskopie metody   MeSH
• spektroskopie infračervená s Fourierovou transformací metody   MeSH
• stříbro chemie   MeSH
• testování materiálů MeSH
• transmisní elektronová mikroskopie metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The ecotoxicological effect of after-usage released TiO2 nanoparticles in aquatic resources has been a major concern owing to their production and utilization in different applications. Addressing the issue, this study investigates the detailed in vivo molecular toxicity of TiO2 nanoparticles with Paramecium caudatum. TiO2 nanoparticles were synthesized at a lab scale using high energy ball milling technique; characterized for their physicochemical properties and investigated for their ecotoxicological impact on oxidative stress, steatosis, and apoptosis of cells through different biochemical analysis, flow cytometry, and fluorescent microscopy. TiO2 nanoparticles; TiO2 (N15); of size 36 ± 12 nm were synthesized with a zeta potential of - 20.2 ± 8.8 mV and bandgap of 4.6 ± 0.3 eV and exhibited a blue shift in UV-spectrum. Compared to the Bulk TiO2, the TiO2 (N15) exhibited higher cytotoxicity with a 24 h LC50 of 202.4 μg/ml with P. Caudatum. The mechanism was elucidated as the size and charge-dependent internalization of nanoparticles leading to abnormal physiological metabolism in oxidative stress, steatosis, and apoptosis because of their influential effect on the activity of metabolic proteins like SOD, GSH, MDA, and catalase. The study emphasized the controlled usage TiO2 nanoparticles in daily activity with a concern for ecological and biomedical aspects.

• MeSH
• apoptóza MeSH
• nanočástice * chemie   toxicita   MeSH
• oxidační stres MeSH
• Paramecium caudatum * MeSH
• titan toxicita   MeSH
• Publikační typ
• časopisecké články MeSH

The crystallization of poorly soluble drug molecules with an excipient into new solid phases called cocrystals has gained a considerable popularity in the pharmaceutical field. In this work, the cocrystal approach was explored for a very poorly water soluble antifungal active, itraconazole (ITR), which was, for the first time, successfully converted into this multicomponent solid using an aromatic coformer, terephthalic acid (TER). The new cocrystal was characterized in terms of its solid-state and structural properties, and a panel of pharmaceutical tests including wettability and dissolution were performed. Evidence of the cocrystal formation was obtained from liquid-assisted grinding, but not neat grinding. An efficient method of the ITR-TER cocrystal formation was ball milling. The stoichiometry of the ITR-TER phase was 2:1 and the structure was stabilized by H-bonds. When comparing ITR-TER with other cocrystals, the intrinsic dissolution rates and powder dissolution profiles correlated with the aqueous solubility of the coformers. The rank order of the dissolution rates of the active pharmaceutical ingredient (API) from the cocrystals was ITR-oxalic acid > ITR-succinic acid > ITR-TER. Additionally, the ITR-TER cocrystal was stable in aqueous conditions and did not transform to the parent drug. In summary, this work presents another cocrystal of ITR that might be of use in pharmaceutical formulations.

• Publikační typ
• časopisecké články MeSH