In our theoretical study, the enhanced solubility of CuO nanoparticles in water saturated by air is predicted based on a simple thermodynamic model. CuO is considered in the form of nanoparticles with various shapes. The interfacial energy of a solid CuO/dilute aqueous solution interface was assessed by applying the average CuO surface energy and contact angle of a sessile drop of water. The equilibrium CuO solubility was calculated using Gibbs energy minimization technique. For the smallest spherical nanoparticles considered in this work (r = 2 nm), the solubility is significantly higher than the solubility of bulk material. In the case of cylindrical nanoparticles, the solubility increase is even more considerable. The CuO spherical nanoparticles solubility was also calculated using the Ostwald-Freundlich equation which is known to overestimate the solubility as discussed in this contribution.

• Klíčová slova
• CuO, Ostwald–Freundlich equation, nanoparticles, solubility, thermodynamics,
• Publikační typ
• časopisecké články MeSH

Nanoparticles can be considered as a useful tool for improving properties of poorly soluble active ingredients. Hydrochlorothiazide (Class IV of the Biopharmaceutical Classification System) was chosen as a model compound. Antisolvent precipitation-solvent evaporation and emulsion solvent evaporation methods were used for preparation of 18 samples containing hydrochlorothiazide nanoparticles. Water solutions of surfactants sodium dodecyl sulfate, Tween 80 and carboxymethyl dextran were used in mass concentrations of 1%, 3% and 5%. Acetone and dichloromethane were used as solvents of the model compound. The particle size of the prepared samples was measured by dynamic light scattering. The selected sample of hydrochlorothiazide nanoparticles stabilized with carboxymethyl dextran sodium salt with particle size 2.6 nm was characterized additionally by Fourier transform mid-infrared spectroscopy and scanning electron microscopy. It was found that the solubility of this sample was 6.5-fold higher than that of bulk hydrochlorothiazide.

• Klíčová slova
• dynamic light scattering, hydrochlorothiazide, infrared spectroscopy, nanoparticles, scanning electron microscopy, solubility,
• MeSH
• dynamický rozptyl světla MeSH
• hydrochlorthiazid chemická syntéza   chemie   MeSH
• molekulární struktura MeSH
• nanočástice chemie   MeSH
• povrchově aktivní látky chemie   MeSH
• příprava léků metody   MeSH
• rozpouštědla chemie   MeSH
• rozpustnost MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hydrochlorthiazid MeSH
• povrchově aktivní látky MeSH
• rozpouštědla MeSH

A pair of popular thermodynamic models for pharmaceutical applications, namely, the perturbed-chain statistical associating fluid theory (PC-SAFT) equation of state and the conductor-like screening model for real solvents (COSMO-RS) are thoroughly benchmarked for their performance in predicting the solubility of active pharmaceutical ingredients (APIs) in pure solvents. The ultimate goal is to provide an illustration of what to expect from these progressive frameworks when applied to the thermodynamic solubility of APIs based on activity coefficients in a purely predictive regime without specific experimental solubility data (the fusion properties of pure APIs were taken from experiments). While this kind of prediction represents the typical modus operandi of the first-principles-aided COSMO-RS, PC-SAFT is a relatively highly parametrized model that relies on experimental data, against which its pure-substance and binary interaction parameters (kij) are fitted. Therefore, to make this benchmark as fair as possible, we omitted any binary parameters of PC-SAFT (i.e., kij = 0 in all cases) and preferred pure-substance parameter sets for APIs not trained to experimental solubility data. This computational approach, together with a detailed assessment of the obtained solubility predictions against a large experimental data set, revealed that COSMO-RS convincingly outperformed PC-SAFT both qualitatively (i.e., COSMO-RS was better in solvent ranking) and quantitatively, even though the former is independent of both substance- and mixture-specific experimental data. Regarding quantitative comparison, COSMO-RS outperformed PC-SAFT for 9 of the 10 APIs and for 63% of the API-solvent systems, with root-mean-square deviations of the predicted data from the entire experimental data set being 0.82 and 1.44 log units, respectively. The results were further analyzed to expand the picture of the performance of both models with respect to the individual APIs and solvents. Interestingly, in many cases, both models were found to qualitatively incorrectly predict the direction of deviations from ideality. Furthermore, we examined how the solubility predictions from both models are sensitive to different API parametrizations.

• Klíčová slova
• COSMO-RS, PC-SAFT, benchmark, pharmaceuticals, prediction, solubility,
• MeSH
• léčivé přípravky MeSH
• rozpouštědla MeSH
• rozpustnost * MeSH
• termodynamika MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• léčivé přípravky MeSH
• rozpouštědla MeSH

Knowledge of the active pharmaceutical ingredient (API) solubility in a polymer is imperative for successful amorphous solid dispersion design and formulation but acquiring this information at storage temperature is challenging. Various solubility determination methods have been established, which utilize differential scanning calorimetry (DSC). In this work, three commonly used DSC-based protocols [i.e., melting point depression (MPD), recrystallization, and zero-enthalpy extrapolation (Z-EE)] and a method that we have developed called "step-wise dissolution" (S-WD) were analyzed. For temperature-composition phase diagram construction, two glass-transition temperature equations (i.e., those of Gordon-Taylor and Kwei) and three solid-liquid equilibrium curve modeling approaches [i.e., the Flory-Huggins model, an empirical equation, and the perturbed-chain statistical associating fluid theory (PC-SAFT) equation of state (EOS)] were considered. Indomethacin (IND) and Kollidon 12 PF (PVP K12) were selected as the API and polymer, respectively. An annealing time investigation revealed that the IND-PVP K12 dissolution process was remarkably faster than demixing, which contradicted previously published statements. Thus, the recrystallization method overestimated the solubility of IND in PVP K12 when a 2-h time of annealing was set as the benchmark. Likewise, the MPD and Z-EE methods overestimated the API solubility because of unreliable IND melting endotherm evaluation at lower API loadings and a relatively slow heating rate, respectively. When the experimental results obtained using the S-WD method (in conjunction with the Kwei equation) were applied to the PC-SAFT EOS, which was regarded as the most reliable combination, the predicted IND solubility in PVP K12 at T = 25 °C was approximately 40 wt %. When applicable, the S-WD method offers the advantage of using a limited number of DSC sample pans and API-polymer physical mixture compositions, which is both cost- and time-effective.

• Klíčová slova
• PC-SAFT, amorphous solid dispersion, differential scanning calorimetry, phase diagram, solid−liquid equilibrium, solubility,
• MeSH
• chemické modely MeSH
• chemie farmaceutická metody   MeSH
• diferenciální skenovací kalorimetrie MeSH
• krystalizace MeSH
• polymery chemie   MeSH
• pomocné látky chemie   MeSH
• rozpustnost MeSH
• tranzitní teplota MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• polymery MeSH
• pomocné látky MeSH

The massive increase in the use of PET plastic bottles has raised the challenge of accumulated waste plastics disposal and its related environmental concerns. Reusing this plastic waste through a solvent-based recycling process seems to be an eco-friendly solution for eliminating waste plastic and converting them into high quality products. The selection of solvent with its temperature requirement for the dissolution of polymeric materials is crucial in the solvent-based recycling process. Therefore, an innovative MATLAB program named HSPs-TPT was designed and constructed in this work to evaluate the dissolving power of solvents. Through this program, the solubility of the waste PET polymer was examined in thirteen (13) different solvents at different temperatures. As a results, the degree of waste PET polymer dissolution in the solvents was presented as the polymer-solvent solubility diagram, which provided the information about the relative energy difference (RED) change with the temperature rise. The program also provided the temperature range effective for the dissolution of PET by indicating the minimum and maximum solubility point for each solvent, which was further validated by the experimental data found in the literature. The proposed MATLAB program can numerically analyse the solubility of a polymer in different solvents in a short time for the recycling process and fabrication of different value-added plastic products such as polymer monoliths and membrane filters.

• Klíčová slova
• Hansen solubility, Membrane, Model analysis, Polyethylene terephthalate (PET), Waste,
• MeSH
• plastické hmoty * MeSH
• polyethylentereftaláty * MeSH
• recyklace MeSH
• rozpouštědla MeSH
• rozpustnost MeSH
• teplota MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• plastické hmoty * MeSH
• polyethylentereftaláty * MeSH
• rozpouštědla MeSH

In drug development, preformulation is the key step, where compatibility between active pharmaceutical ingredient (API) and excipients is the crucial parameter. To simplify this process, reliable and suitable prediction models are needed. In this case, Hansen solubility parameters (HSPs) can be used. Moreover, HSPs can also describe and characterize the surface properties of the measured substances. Precisely, the surface properties of APIs and excipients affect the compatibility of the resulting dosage form. In this work, HSPs of six selected APIs of different chemical nature were determined (tadalafil, vardenafil-hydrochloride trihydrate, mefenamic acid, bisoprolol hemi-fumarate, meloxicam and indomethacin) using inverse gas chromatography (IGC) according to Snyder and Karger adsorption model. This study aimed to investigate the influence of APIs structure on HSPs and to prove the sensitivity of this method to different chemical nature of measured substances. Our results showed the influence of selected APIs chemical nature on HSPs. These results can provide a better understanding of API behaviour during the drug development process.

• Klíčová slova
• Compatibility, Energy of adsorption, Hansen solubility parameters, Inverse gas chromatography, Snyder and Karger adsorption model, van Krevelen,
• MeSH
• chromatografie plynová MeSH
• indomethacin * MeSH
• pomocné látky * MeSH
• povrchové vlastnosti MeSH
• rozpustnost MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• indomethacin * MeSH
• pomocné látky * MeSH

Water solubility is one of the key features of potential therapeutic agents. In order to enhance the low water solubility of the parent 5-butyl-4-(4-methoxyphenyl)-6-phenylpyrimidin-2-amine, a potent inhibitor of prostaglandin E2 (PGE2 ) production, we synthesized and evaluated a new series of derivatives in which the butyl group at the C5 position of the pyrimidine ring was replaced with a less lipophilic substituent, preferably with a hydrophilic aliphatic moiety. Except for the 5-cyanopyrimidine derivative, all target compounds exhibited increased (2.7-87-fold) water solubility relative to the parent compound. Although nontoxic in mouse peritoneal cells, the prepared compounds were either equipotent or weaker inhibitors of PGE2 production than the parent compound. The most promising compound from the series was found to be the 5-(2,5,8,11-tetraoxadodecyl)pyrimidine derivative (with three polyethylene glycol units at the C5 position), which exhibited 32-fold higher water solubility and only slightly weaker inhibitory activity (22 % of remaining PGE2 production) compared with the parent compound (15 % of remaining PGE2 production).

• Klíčová slova
• anti-inflammatory, prostaglandin E2, pyrimidines, solubility, synthesis,
• MeSH
• buněčné linie MeSH
• dinoproston antagonisté a inhibitory   metabolismus   MeSH
• molekulární struktura MeSH
• myši MeSH
• pyrimidiny chemická syntéza   chemie   farmakologie   MeSH
• rozpustnost MeSH
• voda chemie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dinoproston MeSH
• pyrimidiny MeSH
• voda MeSH

Metallacarborane moieties have been identified as promising pharmacophores. The pharmaceutical use of such compounds is, however, complicated by their low solubility and tendency to self-assemble in aqueous solution. In this work, we estimated the solubilities of a vast series of metallacarboranes [cobalt bis(dicarbollide) derivatives] in pure water, saline, and saline with human serum albumin as a model of blood plasma. In addition, we determined the octanol-water partition coefficients (Pow) as a lipophilicity descriptor. Pow weakly correlates with the water solubility of metallacarboranes, whereas the ability of HSA to increase the solubility of metallacarboranes correlates well with their Pow values. Because metallacarboranes are known inhibitors of HIV protease, the possible correlation between Pow and the ability to inhibit HIV protease was investigated. Results from this study indicate that interaction of metallacarborane inhibitors with HIV protease is driven by specific binding rather than by promiscuous lipophilic interactions. The most promising candidates for further drug development were identified by ligand lipophilicity efficiency analysis.

• MeSH
• inhibitory HIV-proteasy chemie   farmakologie   MeSH
• kobalt chemie   farmakologie   MeSH
• lidé MeSH
• ligandy MeSH
• lipidy chemie   MeSH
• molekulární struktura MeSH
• objevování léků MeSH
• organokovové sloučeniny chemie   farmakologie   MeSH
• rozpustnost MeSH
• sérový albumin chemie   MeSH
• sloučeniny boru chemie   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• inhibitory HIV-proteasy MeSH
• kobalt MeSH
• ligandy MeSH
• lipidy MeSH
• organokovové sloučeniny MeSH
• sérový albumin MeSH
• sloučeniny boru MeSH

This paper describes a method for determination of the diffusion coefficient and the solubility of radon in plastics. The method is based on the absorption and desorption of radon in plastics. Firstly, plastic specimens are exposed for controlled time to referent (222)Rn concentrations. After exposure, the activity of the specimens is followed by HPGe gamma spectrometry. Using the mathematical algorithm described in this report and the decrease of activity as a function of time, the diffusion coefficient can be determined. In addition, if the referent (222)Rn concentration during the exposure is known, the solubility of radon can be determined. The algorithm has been experimentally applied for different plastics. The results show that this approach allows the specified quantities to be determined with a rather high accuracy-depending on the quality of the counting equipment, it can be better than 10 %.

• MeSH
• algoritmy MeSH
• difuze MeSH
• lidé MeSH
• matematika MeSH
• monitorování radiace * MeSH
• plastické hmoty analýza   MeSH
• radon analýza   chemie   MeSH
• rozpustnost MeSH
• spektrometrie gama MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• plastické hmoty MeSH
• radon MeSH

In recent years there has been a growing interest in formulating solid dispersions, which purposes mainly include solubility enhancement, sustained drug release and taste masking. The most notable problem by these dispersions is drug-carrier (in)solubility. Here we focus on solubility parameters as a tool for predicting the solubility of a drug in certain carriers. Solubility parameters were determined in two different ways: solely by using calculation methods, and by experimental approaches. Six different calculation methods were applied in order to calculate the solubility parameters of the drug ibuprofen and several excipients. However, we were not able to do so in the case of ibuprofen lysinate, as calculation models for salts are still not defined. Therefore, the extended Hansen's approach and inverse gas chromatography (IGC) were used for evaluating of solubility parameters for ibuprofen lysinate. The obtained values of the total solubility parameter did not differ much between the two methods: by the extended Hansen's approach it was δt = 31.15 MPa(0.5) and with IGC it was δt = 35.17 MPa(0.5). However, the values of partial solubility parameters, i.e., δd, δp and δh, did differ from each other, what might be due to the complex behaviour of a salt in the presence of various solvents.

• Klíčová slova
• Hansen’s solubility parameters, extended Hansen’s approach, ibuprofen, ibuprofen lysinate, inverse gas chromatography,
• MeSH
• antiflogistika nesteroidní chemie   MeSH
• chromatografie plynová MeSH
• farmaceutická technologie metody   MeSH
• ibuprofen analogy a deriváty   chemie   MeSH
• lysin analogy a deriváty   chemie   MeSH
• nosiče léků MeSH
• pomocné látky chemie   MeSH
• rozpouštědla chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antiflogistika nesteroidní MeSH
• ibuprofen MeSH
• lysin MeSH
• nosiče léků MeSH
• pomocné látky MeSH
• rozpouštědla MeSH
• solufenum MeSH Prohlížeč