Phenothiazines solution complexity - determination of pKa and solubility-pH profiles exhibiting sub-micellar aggregation at 25 and 37°C

The ionization constants (pKa) and the pH-dependent solubility (log S-pH) of six phenothiazine derivatives (promazine hydrochloride, chlorpromazine hydrochloride, triflupromazine hydrochloride, fluphenazine dihydrochloride, perphenazine free base, and trifluoperazine dihydrochloride) were determined at 25 and 37 °C. The pKa values of these low-soluble surface active molecules were determined by the cosolvent method (n-propanol/water at 37 °C and methanol/water at 25 °C). The log S-pH profiles were measured at 24 h incubation time in 0.15 M phosphate buffers. The log S-pH "shape-template" method, which critically depends on accurate pKa values (determined independently of solubility data), was used to propose speciation models, which were subsequently refined by rigorous mass-action weighted regression procedure described recently. Differential scanning calorimetry (DSC), UV-visible spectrophotometry, potentiometric, and high performance liquid chromatography (HPLC) measurements were used to characterize the compounds. The intrinsic solubility (S0) values of the three least-soluble drugs (chlorpromazine·HCl, triflupromazine·HCl, and trifluoperazine·2HCl) at 25 °C were 0.5, 1.1, and 2.7 μg/mL (resp.). These values increased to 5.5, 9.2, and 8.7 μg/mL (resp.) at the physiological temperature. The enthalpies of solution for the latter compounds were exceptionally high positive (endothermic) values (99-152 kJ·mol− 1). Cationic sub-micellar aggregates were evident (from the distortions in the log S-pH profiles) for chlorpromazine, fluphenazine, perphenazine, and trifluoperazine at 25 °C. The effects persisted at 37 °C for chlorpromazine and trifluoperazine. The solids in suspension were apparently amorphous in cases where the drugs were introduced as the chloride salts

Effect of 2-Hydroxypropyl-β-cyclodextrin on Solubility of Sparingly Soluble Drug Derivatives of Anthranilic Acid

Guest-host complex formation of three drug derivatives of anthranilic acid, mefenamic acid, niflumic acid, and flufenamic acid with 2-hydroxypropyl-β-cyclodextrin (2HP-β-CD) in aqueous solutions was investigated using “Phase solubility study” with UV-vis spectrophotometry. Solubility of sparingly soluble drugs has been improved by addition of 2HP-β-CD at two temperatures 298.15 K and 310.15 K and two pH values 2 and 7. The influence of different 2HP-β-CD concentration on solubility of drugs at different pH and temperatures has been investigated. The 2HP-β-CD-drug complex stability constants (Ks), and dissociations constants (Kd), as well as the thermodynamic parameters of reaction, i.e., the free energy change (ΔG), the enthalpy change (ΔH) and the entropy change (ΔS), were determined. The experimental data indicated formation of 1:1 inclusion complexes, which were found effective binders increasing the solubility of drugs

Pilot Test on Pre-Swim Hygiene as a Factor Limiting Trihalomethane Precursors in Pool Water by Reducing Organic Matter in an Operational Facility

Pool water must be constantly disinfected. Chlorine compounds used to disinfect pools react with organic substances such as sweat, urine, and personal care products introduced into pool water by users and results in the formation of disinfection byproducts. Trihalomethanes (THM), including chloroform and dissolved organic carbon (DOC) concentrations, were quantified using a two-stage process: determining initial THM and chloroform levels; then searching for a cheap and easy-to-use method to improve water quality. The method proposed here to limit THM and DOC concentrations in water is controlled showering. At three swimming pool facilities, chloroform concentrations (13.8 ± 0.33 µg/L, 15.5 ± 0.44 µg/L, and 13.9 ± 0.06 µg/L) were below the threshold concentration of 30 μg/L. At a fourth facility, however, the chloroform concentration exceeded that threshold (40.7 ± 9.68 μg/L) when showering was not controlled. Those conditions improved after the introduction of a mandatory shower; concentrations of DOC, THMs, and chloroform all decreased. The chloroform concentration decreased to 29.4 ± 3.8 μg/L, the THM concentration was 31.3 ± 3.9 μg/L, and the DOC concentration was 6.09 ± 0.05 mg/L. Pilot tests were carried out at real facilities to determine whether the control of pre-swim hygiene was possible. The introduction of proper pre-swim hygiene limited the concentration of DOC in water and can lead to a healthier environment for everyone attending the swimming facility

Formulacja nanocząstek polilaktyd/poli(kwas mlekowy-co-glikolowy) z nimesulidem oraz ocena kinetyki ich uwalniania

Polymeric nanoparticles containing nimesulide (NIM) were prepared by the emulsion solvent evaporation method. Biodegradable polymers were used as materials for nanoparticle formulations with the application of studies for the drug delivery sector in mind. Two analytical methods, scanning electron microscopy (SEM) and particle size analysis, were applied to investigate the obtained nanoparticles. Characteristic parameters were calculated to describe the amount of active pharmaceutical ingredient trapped in nanoparticles. The biological active substance release process was investigated under different conditions. The impact of various parameters [kind of polymer (PLA or PLGA), speed of mixing and especially of pH] is presented across our research.Polimerowe nanocząstki zawierające nimesulid (NIM) otrzymano metodą emulsyjną z odparowaniem rozpuszczalnika. Do ich wytworzenia wykorzystano biodegradowalne polimery. Wytworzone nanocząstki zbadano za pomocą skaningowej mikroskopii elektronowej (SEM) oraz analizatora wielkości cząstek. Obliczono charakterystyczne parametry opisujące ilość substancji farmaceutycznie aktywnej uwięzionej wewnątrz nanocząstek. Oceniono wpływ rodzaju polimeru stosowanego do kapsułkowania, szybkości mieszania suspensji, w szczególności pH środowiska na proces uwalniania substancji biologicznie czynnej

Analysis of the Kinetics of Swimming Pool Water Reaction in Analytical Device Reproducing Its Circulation on a Small Scale

The most common cause of diseases in swimming pools is the lack of sanitary control of water quality; water may contain microbiological and chemical contaminants. Among the people most at risk of infection are children, pregnant women, and immunocompromised people. The origin of the problem is a need to develop a system that can predict the formation of chlorine water disinfection by-products, such as trihalomethanes (THMs). THMs are volatile organic compounds from the group of alkyl halides, carcinogenic, mutagenic, teratogenic, and bioaccumulating. Long-term exposure, even to low concentrations of THM in water and air, may result in damage to the liver, kidneys, thyroid gland, or nervous system. This article focuses on analysis of the kinetics of swimming pool water reaction in analytical device reproducing its circulation on a small scale. The designed and constructed analytical device is based on the SIMATIC S7-1200 PLC driver of SIEMENS Company. The HMI KPT panel of SIEMENS Company enables monitoring the process and control individual elements of device. Value of the reaction rate constant of free chlorine decomposition gives us qualitative information about water quality, it is also strictly connected to the kinetics of the reaction. Based on the experiment results, the value of reaction rate constant was determined as a linear change of the natural logarithm of free chlorine concentration over time. The experimental value of activation energy based on the directional coefficient is equal to 76.0 [kJ×mol−1]. These results indicate that changing water temperature does not cause any changes in the reaction rate, while it still affects the value of the reaction rate constant. Using the analytical device, it is possible to constantly monitor the values of reaction rate constant and activation energy, which can be used to develop a new way to assess pool water quality

Production of 2-phenylethanol (PEA) by yeast with ionic liquids in situ extraction

Zbadano następujące ciecze jonowe: bis(trifluorometylosulfonylo) imidek N-oktylo-izochinolinowy [C8iQuin][NTf2], bis(trifluorometylosulfonylo)imidek butylometylo-pyrrolidyniowy [BMPyr][NTf2], tricyjanometan triheksylotetradecylofosfoniowy [P6,6,6,14][TCM], bis(trifluorometylosulfonylo)imidek 1-metylo-1-heksylopiperydyniowy [HMPIP][NTf2] jako potencjalne ekstrahenty in situ dla 2-fenyloetanolu, produkowanego przez drożdże Saccharomyces cerevisiae AM1d. Najlepsze wyniki otrzymano dla [BMPyr][NTf2].Ionic liquids were examined as follows: N-hexylisoquinolinium bis(trifluroromethylsulfonyl)imide [C8iQuin][NTf2], 1-butyl-1-methylpyrrolidinium bis(trifluroromethylsulfonyl) imide [BMPyr][NTf2], trihexyltetradecylphosphonium tricyanomethanide [P6,6,6,14][TCM], 1-hexyl-1-methylpiperidinium bis(trifluroromethylsulfonyl)imide [HMPIP][NTf2] as a potential extractants in situ for 2-phenylethanol produced by Saccharomyces cerevisiae AM1-d. The best results were obtained for [BMPyr][NTf2]