The aim of this paper was to evaluate physical stability of solid dispersions in respect to the drug, tadalafil (Td), in vinylpyrrolidone and vinyl acetate block copolymer (PVP-VA). Nine solid dispersions of Td in PVP-VA (Td/PVP-VA) varied in terms of quantitative composition (1:9-9:1, w/w) were successfully produced by spray-drying. Their amorphous nature, supersaturated character and molecular level of mixing (a solid solution structure) were subsequently confirmed using DSC, PXRD, SEM and calculation of Hansen total solubility parameters. Due to thermal degradation of both components before the melting point of Td (302.3°C), an approach based on the drug crystallization from the supersaturated solid dispersion was selected to calculate the solubility of Td in the polymer. Annealing of the Td/PVP-VA solid dispersion (1:1, w/w) at selected temperatures above its Tg resulted in different stable solid dispersions. According to the Gordon-Taylor equation their new Tgs gave the information about the quantitative composition which corresponded to the thermodynamic solubility of Td in PVP-VA at given temperatures of annealing. The obtained relationship was fitted to the exponential function, with the calculated solubility of Td of 20.5% at 25°C. This value was in accordance with the results of hot stage polarizing light microscopy as well as stability tests carried out at 80°C and 0% RH, in which Td solid dispersions containing 10-20% of the drug were the only systems that did not crystallize within two months. A thermal analysis protocol utilizing a fast heating rate was shown to generate Td solubility data complementing the solid dispersion method. The Flory-Huggins model applied for the Td/PVP-VA system yielded the solubility value of 0.1% at 25°C, showing the lack of applicability in this case.

Lipophilicity is a vital physicochemical parameter of a molecule, which affects several biological processes such as absorption, tissue distribution, and pharmacokinetic properties. In this study, evaluation of lipophilicities of a series of novel fluoroquinolone-Safirinium dye hybrids using chromatographic and computational methods is presented. Fluoroquinolone-Safirinium dye hybrids have been synthesized as new dual-acting hydrophilic antibacterial agents. Reversed phase thin-layer chromatography and micellar electrokinetic chromatography experiments were carried out. Furthermore, logP values of the target structures were predicted by means of different software platforms and algorithms. In order to assess similarities and dissimilarities of the obtained lipophilicity indexes, cluster analysis and sum of ranking differences were performed. The significant differences of calculated logP values (α = 0.05, p < 0.001) indicated that an experimental approach is necessary for lipophilicity prediction of this class of antibiotics. Chromatographic data indicated that the newly synthesized hybrid (fluoro)quinolone-based quaternary ammonium derivatives show less lipophilic character than the parent (fluoro)quinolones. Additionally, the chromatographically obtained lipophilicity indexes were evaluated for possible application in quantitative retention–activity relationships. The established lipophilicity models have the potential to predict antimicrobial activities of a series of quaternary (fluoro)quinolones against Bacillus subtilis, Escherichia coli, and Proteus vulgaris.

Owing to their excellent antimicrobial activities with a relatively low cost of production, lipopeptides are being intensively investigated as potential alternatives to popular antimicrobials. However, a critical obstacle for their application is a relatively high toxicity, hence a lot of attention has been paid to designing new molecules with optimal properties. In this study we synthesized the following lipopeptides: C₁₆-KK-NH₂, C₁₆-KεK-NH₂, C₁₆-KKK-NH₂, C₁₆-KRK-NH₂, C₁₆-RR-NH₂, C₁₆-RRR-NH₂, (C₁₀)₂-KKKK-NH₂ and (C₁₂)₂-KKKK-NH₂. Their antimicrobial activity against representative strains of Gram-positive bacteria, Gram-negative bacteria and fungi has been confirmed. The compounds have been evaluated with regard to the safety of their application in dermatology. The cytotoxicity was determined in HaCaT keratinocytes using MTT assay, whereas Strat M membranes placed in Franz diffusion cells were used to assess their ability to skin permeation. The compounds containing one hexadecanoic acid chain turned out to be very toxic towards human keratinocytes, while lipopeptides containing two fatty acid chains (decanoic and dodecanoic) demonstrated much lower cytotoxicity. For the most promising lipopeptide, (C₁₀)₂-KKKK-NH₂, the measured IC₅₀ on HaCaT keratinocytes was few times higher as compared to MICs obtained for the tested bacteria. Both groups of lipopeptides did not permeate the model membranes and therefore lack of permeation through human skin could be expected. The results of this work encourage further research on the potential application of lipopeptides with two fatty acids as novel antimicrobials.

The purpose of this paper is to examine the physical stability as well as viscoelastic properties of the binary amorphous ezetimibe–simvastatin system. According to our knowledge, this is the first time that such an amorphous composition is prepared and investigated. The tendency toward re-crystallization of the amorphous ezetimibe–simvastatin system, at both standard storage and elevated temperature conditions, have been studied by means of X-ray diffraction (XRD). Our investigations have revealed that simvastatin remarkably improves the physical stability of ezetimibe, despite the fact that it works as a plasticizer. Pure amorphous ezetimibe, when stored at room temperature, begins to re-crystallize after 14 days after amorphization. On the other hand, the ezetimibe-simvastatin binary mixture (at the same storage conditions) is physically stable for at least 1 year. However, the devitrification of the binary amorphous composition was observed at elevated temperature conditions (T = 373 K). Therefore, we used a third compound to hinder the re-crystallization. Finally, both the physical stability as well as viscoelastic properties of the ternary systems containing different concentrations of the latter component have been thoroughly investigated.

Sulfonamides are a classic group of chemotherapeutic drugs with a broad spectrum of pharmacological action, including anticancer activity. In this work, reversed-phase high-performance liquid chromatography and biomimetic chromatography were applied to characterize the lipophilicity of sulfonamide derivatives with proven anticancer activities against human colon cancer. Chromatographically determined lipophilicity parameters were compared with obtained logP, employing various computational approaches. Similarities and dissimilarities between experimental and computational logP were studied using principal component analysis, cluster analysis, and the sum of ranking differences. Furthermore, quantitative structure–retention relationship modeling was applied to understand the influences of sulfonamide’s molecular properties on lipophilicity and affinity to phospholipids.

The widespread use of biomaterials such as contact lenses is associated with the development of biofilm-related infections which are very difficult to manage with standard therapies. The formation of bacterial biofilms on the surface of biomaterials is associated with increased antibiotic resistance. Owing to their promising antimicrobial potential, lipopeptides are being intensively investigated as novel antimicrobials. However, due to the relatively high toxicity exhibited by numerous compounds, a lot of attention is being paid to designing new lipopeptides with optimal biological activities. The principal aim of this study was to evaluate the potential ophthalmic application of lipopeptide (C₁₀)₂-KKKK-NH₂. This lipopeptide was synthesized according to Fmoc chemistry using the solid-phase method. The antibiofilm activities of the lipopeptide, antibiotics used in ocular infections, and commercially available lens liquids were determined using the broth dilution method on polystyrene 96-well plates and contact lenses. Resazurin was applied as the cell-viability reagent. The effectiveness of the commercially available lens liquids supplemented with the lipopeptide was evaluated using the same method and materials. (C₁₀)₂-KKKK-NH₂ exhibited stronger anti-biofilm properties compared to those of the tested conventional antimicrobials and showed the ability to enhance the activity of lens liquids at relatively low concentrations (4–32 mg/L). Estimation of the eye irritation potential of the lipopeptide using Toxtree software 2.6.13 suggests that the compound could be safely applied on the human eye. The results of performed experiments encourage further studies on (C₁₀)₂-KKKK-NH₂ and its potential application in the prophylaxis of contact lens-related eye infections.