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•Grinding as eco-friendly method to improve the praziquantel solubility was proposed.•Liquid assisted grinding gained in cocrystals with pH dependent solubility.•Neat grinding gained ...in highly soluble amorphous cyclodextrin complexes.•Cocrystal formation impaired the chemical stability of drug.•Cyclodextrin complexation did not change intrinsically high drug permeability.
Mechanochemical activation using several different co-grinding additives was applied as a green chemistry approach to improve physiochemical and biopharmaceutical properties of praziquantel (PZQ). Liquid assisted grinding with an equimolar amount of citric acid (CA), malic acid (MA), salicylic acid (SA) and tartaric acid (TA) gained in cocrystal formation, which all showed pH-dependent solubility and dissolution rate. However, the most soluble cocrystal of PZQ with MA was chemically unstable, as seen during the stability testing. Equimolar cyclodextrin complexes prepared by neat grinding with amorphous hydroxypropyl-β-cyclodextrin (HPβCD) and randomly methylated β-cyclodextrin (MEβCD) showed the highest improvement in drug solubility and the dissolution rate, but only PZQ/HPβCD product presented an acceptable chemical and photostability profile. A combined approach, by co-grinding the drug with both MA and HPβCD in equimolar ratio, also gave highly soluble amorphous product which again was chemical instable and therefore not suitable for the pharmaceutical use. Studies on Caco-2 monolayer confirmed the biocompatibility of PZQ/HPβCD complex and showed that complexation did not adversely affect the intrinsically high PZQ permeability (Papp(PZQ)=(3.72±0.33)×10−5cms−1 and Papp(PZQ/HPβCD)=(3.65±0.21)×10−5cms−1; p>0.05). All this confirmed that the co-grinding with the proper additive is as a promising strategy to improve biopharmaceutical properties of the drug.
is used in herbal medicinal products for the prevention and treatment of the common cold, as well as for skin disorders and minor wounds. In this study, the efficiency of traditional maceration using ...water and ethanol was compared with the maceration using mixtures of water and glycerol, a non-toxic, biodegradable solvent from renewable sources. It was found that the glycerol-water mixtures were as effective as ethanol/water mixtures for the extraction of caffeic acid derivatives. All the prepared extracts demonstrated notable antiradical properties. Furthermore, an efficient ultrasound-assisted extraction using glycerol-water mixtures was developed using six independent variables. Their levels needed for the maximum extraction of caffeic acid derivatives were as follows: glycerol 90% (
), temperature 70 °C, ultrasound power 72 W, time 40 min, and ascorbic acid 0 mg/mL. Under the optimized conditions, ultrasound-assisted extraction was superior to maceration. It achieved significantly higher yields of phenolic acids in shorter extraction time. The presence of zinc in plant material may contribute to the beneficial effects of
preparations. Since glycerol is a non-toxic solvent with humectant properties, the prepared extracts can be directly used for the preparation of cosmetics or oral pharmaceutical formulations without the need for solvent removal.
The purpose of the research was to measure the increase in the binding of inclusion complexes β-cyclodextrin-peppermint oil (β-CD_PM) to cellulose in cotton and cotton/polyester material with BTCA as ...the crosslinking agent by applying an ultrasonic bath at room temperature and a frequency of 80 kHz for 10 min. After sonication, the samples were left in a bath for 24 h after which they were dried, thermocondensed and subjected to a number of wash cycles. The treated samples were analysed with Attenuated total reflection (ATR) units heated up to 300 °C (Golden Gate (FTIR-ATR)) to monitor chemical changes indicative of crosslinking, while physico-chemical changes in the samples were monitored by using Fourier transform infrared spectroscopy (FTIR-ATR). Mechanical properties were measured according to EN ISO 13934-1:1999, and coloristic changes were evaluated by the whiteness degree according to CIE (WCIE) and the yellowing index (YI), while antimicrobial activity was determined according to AATCC TM 147-2016. The results show a physico-chemical modification of the UZV-treated cellulosic material. Moreover, partial antimicrobial efficacy on Gram-negative bacteria was confirmed for treated fabrics.
The research on the possibilities of using biowaste from urban green areas is scarce. In this work, four plants, widely distributed in urban parks in Central Europe (Lotus corniculatus, Medicago ...lupulina, Knautia arvensis and Plantago major) were extracted using eco-friendly solvents based either on aqueous cyclodextrin solutions (hydroxypropyl-β-cyclodextrin or γ-cyclodextrin) or natural deep eutectic solvents based on glycerol, betaine and glucose. Metal content was determined using total reflection X-ray fluorescence (TXRF). The content of selected metabolites was determined using UV-VIS spectrophotometric methods and HPLC. Skin-related bioactivity was assessed using tyrosinase and elastase inhibition assays. The selected plants contained metals beneficial for skin health, such as zinc and calcium, while having a low content of toxic heavy metals. The extracts contained the bioactive phenolics such as quercetin, kaempferol, luteolin and apigenin. L. corniculatus was the most potent tyrosinase inhibitor, while K. arvensis showed the most pronounced elastase inhibitory activity. The employed solvents actively contributed to the observed bioactivity. The results indicate that the biowaste obtained from urban parks represents an ecologically acceptable alternative to conventional cultivation for the preparation of ecologically acceptable, high-value cosmetic products.
The aim of the present study was to explore impact of endurance exercise on urinary level of minerals and trace elements as well as on some oxidative stress and biochemical parameters. Urine samples ...were collected from participants (n=21) of mountain ultra-marathon race (53km; Medvednica, Zagreb, Croatia), before (baseline value), immediately after, 12h and 24h after the race. In urine samples level of minerals (Ca, P, K and Na) and trace elements (Se, Zn, Mn, Cu, Fe and Co) were assessed using the bench top Total reflection X-ray Fluorescence (TXRF) spectrometer. Oxidative stress was determined as level of malondialdehyde (MDA). Immediately after the race level of minerals, trace elements, MDA, creatinine, ketones, erythrocytes and specific gravity increased compared to their baseline value. In 24h follow-up trace elements involved in antioxidant defence, MDA and biochemical parameters returned to their baseline values, Cu and Co remained increased as after the race, Fe and K tended to return to baseline values while Ca, P and Na continued to increase. Mountain ultra-marathon resulted in alteration of physiologically important minerals and trace elements that for some minerals and trace elements persist, indicating their involvement in recovery processes. However, due to their loss in urine, level of minerals and trace elements in athletes participating in endurance exercise should be monitored.
Two
extracts, OPT-1 (rich in phenolic acids) and OPT-2 (rich in total phenols and flavonoids), were prepared using hydroxypropyl-β-cyclodextrin (HP-β-CD)-assisted extraction. The prepared extracts ...were rich in phenolic compounds, including flavonoids and phenolic acids. GC-MS analysis of the extracts identified neryl acetate, neo-intermedeol, β-selinene, γ-curcumene, italidione I, and nerol as the main volatile components of the extracts, as well as plant sterols, γ-sitosterol, campesterol, and stigmasterol. The antioxidant (DPPH radical scavenging, reducing power, and a carotene linoleic acid assay) and cosmeceutical (anti-hyaluronidase, anti-tyrosinase, anti-lipoxygenase, ovalbumin anti-coagulation, and a UV-absorption assay) activity of the extracts in most of the assays was better than the activity of the applied positive controls. Especially low were the IC
values of the extracts in the anti-hyaluronidase (14.31 ± 0.29 μL extract/mL and 19.82 ± 1.53 μL extract/mL for OPT-1 and OPT-2, respectively) and the anti-lipoxygenase (0.96 ± 0.11 μL extract/mL and 1.07 ± 0.01 μL extract/mL for OPT-1 and OPT-2, respectively) assays. The extracts were non-toxic to HaCaT cells in concentrations of up to 62.5 µL extract/mL assuring their status as excellent candidates for cosmeceutical product development appropriate for direct use in cosmetic products without solvent evaporation.
A reliable method for spectrophotometric determination of urinary malondialdehyde (MDA), according to the thiobarbituric acid (TBA) assay, is described. To account for matrix interference and ...differences in individual urine composition, standard addition procedure was applied. The method is adequately selective (LoQ = 0.09 μM in the presence of 0.1 M creatinine and 0.5 M urea) and reliable (within-day and between-day variability of less than 5 %). The mean level of urinary MDA was 1.52 ± 0.73 µM that is in good agreement with spectrofluorometric determination (1.20 ± 0.56 μM; p = 0.085) as well as with previous studies that used HPLC. Furthermore, it is demonstrated that MDA is stabile in urine at room temperature for 24 h and when stored at –20 °C for 6 months. The described method enables simple, rapid and cost-effective determination of urinary MDA as a relevant and non-invasive marker of “whole-body” oxidative stress.
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Type 2 diabetes (T2D) is a chronic disease with a growing prevalence worldwide. In addition to the conventional therapy, many T2D patients use phytotherapeutic preparations. In the present study, ...chemical composition, antioxidant, and α-glucosidase inhibiting activity of traditional antidiabetics from Croatian ethnomedicine (Achillea millefolium, Artemisia absinthium, Centaurium erythraea, Morusalba, Phaseolus vulgaris, Sambucus nigra, and Salvia officinalis) were assessed. The efficacy of water and 80% ethanol as extraction solvents for bioactive constituents was compared. HPLC analysis revealed that the prepared extracts were rich in phenols, especially rutin, ferulic, and chlorogenic acid. Antiradical (against DPPH and ABTS radicals), reducing (towards Mo6+ and Fe3+ ions), and enzyme inhibiting properties were in linear correlation with the content of phenolic constituents. Ethanolic extracts, richer in phenolic substances, showed dominant efficacy in those assays. Aqueous extracts, on the other hand, were better Fe2+ ion chelators and more active in the β-carotene linoleic acid assay. Extracts from S. officinalis and A. millefolium were particularly active antioxidants and α-glucosidase inhibitors. A. absinthium, another potent α-glucosidase inhibitor, contained chromium, a mineral that promotes insulin action. The investigated plants contained significant amounts of minerals useful in management of T2D, with negligible amounts of heavy metals deeming them safe for human use.
Thermal properties of N-carbamoyl benzotriazole derivatives and N,N’,N’’-tribenzyloxyisocyanuric acid were investigated using thermogravimetric analysis and differential scanning calorimetry. The ...results revealed a difference between structural analogs of N-carbamoyl benzotriazole derivatives. They seem to be in agreement with the previously proposed formation of N,N’,N’’-tribenzyloxyisocyanuric acid from 1-(N-benzyloxycarbamoyl) benzotriazole, via an intermediary N-benzyloxyisocyanate acid, during heating. Substantially different thermal properties were observed for structural analogues, 1-(N-methoxycarbamoyl) benzotriazole and 1-(N-ethoxycarbamoyl) benzotriazole. In contrast to N-benzyloxyisocyanate, no corresponding reactions were observed for their decomposition products, i.e., methoxyisocyanate and ethoxyisocyanate.
The aim of this work was to develop Eudragit® S100 (ES100) based pH-responsive microspheres of zaleplon (ZAL) as a potential delivery system for treatment of an insomnia characterised by premature ...awaking and inability to fall asleep again. Microspheres were prepared by spray-drying of ZAL/ES100 dispersion from ethanolic (MS1) or 0.96% aqueous NH4HCO3 solution (MS2). In second case ES100 was first transformed into soluble, thermolabile ammonium salt and then regenerated by an additional thermal treatment at 85°C for 3.5h after spray-drying, as confirmed by FTIR. Preparation from ethanolic medium (MS1) resulted in higher preparation yield (75.14% vs. 56.55%; p<0.05), while in both cases high encapsulation efficiency (91.1 and 95.5%) of drug into microspheres of 1.71–1.76μm was achieved. However, MS1 were characterised by significant drug leaking in the simulated gastric medium (81.7±2.2% of drug dose in 2h), while MS2 formulation released about 24.7±0.5% of ZAL (p<0.01). DSC and XRPD analysis showed that this behaviour could be attributed to a thermally induced ZAL amorphization into ES100 matrix, but also to a sponge-like structure of MS1, while spherical MS2 offered better protection of encapsulated drug. Therefore MS2 were further optimized through addition of Eudragit® NE30D, glyceryl monostearate (GMS) and randomly methylated β-cyclodextrin (RAMEB). The optimal formulation contained ES100, 10% of GMS and 50% of the drug dose in form of inclusion complex with RAMEB, resulting in an acceptable drug release level at pH1.2 of about 10% of the ZAL dose after 2h and a zero-order release (r2>0.98, k=155.0μg/min) at pH6.8.
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•pH-responsive microspheres were prepared by spray-drying of alkaline ES100/ZAL solution.•Additional thermal treatment at 85°C was used to regenerate the ES100 in the insoluble form.•Unwanted ZAL release at pH1.2 was reduced by the addition of 10% GMS.•The ZAL release at pH6.8 was modulated by cyclodextrin complexation of 50% of drug dose.•The optimized formulation presented zero-order drug release kinetic (k0=155μgmin−1).
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