Aim. To study the density and dynamic viscosity of the mixed solvents propylene glycol (PG) – macrogol 400 (M400), to calculate their excess values and excess activation parameters of viscous flow, to evaluate the features of the structure of the mixed solvents and its influence on the in vitro release of PG and M400. Materials and methods. The mixed solvents PG - M400 were studied over the entire concentration range at temperatures from 293.15 to 313.15 K. The density and dynamic viscosity were determined, and the excess density, excess dynamic viscosity, activation parameters of viscous flow, and excess activation parameters of viscous flow were calculated. The in vitro release of PG and M400 from the mixed solvents was studied using vertical diffusion cells. The content of PG and M400 in the receptor medium was determined by gas chromatography using validated analytical procedures. The release rate, cumulative content, percentage of released PG or M400, coefficients of correlation and coefficients of determination were calculated. Results. The isotherms of excess density and excess dynamic viscosity of the mixed solvents PG-M400 pass through a maximum. The enthalpy makes the main contribution to the free activation energy of the viscous flow. The excess free energy is positive and has small values; the values of the excess entropy and excess enthalpy are negative, and the isotherms have the minimum at PG concentrations of 70‑75mol %. The release parameters of M400 are greater in binary mixtures where the M400 structure predominates. At PG content of ~75 mol %, the release parameters for PG and M400 are identical. With the increase in PG content above 75 mol %, when the PG structure predominates in the system, the release parameters of PG increase dramatically, and the release parameters of M400 decrease sharply. Conclusions. The structure of the binary system PG – M400 depends on its composition. Based on the isotherms of excess activation of viscous flow, it is possible to differentiate the areas where the structure of PG or the structure of M400 dominates, or the mixed structure of the binary solvent prevails. The in vitro release parameters for PG and M400 depend on the structure of the mixed solvents. The greatest difference in the release parameters of PG and M400 was observed in the area where the structure of PG dominates

The aim. To identify some factors affecting the in vitro release of ketoprofen from carbomer-based gels. Materials and methods. Carbomer-based gels containing ketoprofen as well as a Newtonian liquid without carbomer, which was the dispersion medium of the gel, were studied by rotational viscometry and spin probe method. The flow behaviour and rheological parameters were determined using the rheograms, and the rotational correlation times of the two dissolved spin probes, the molecules of which contain a carboxyl group or an amino group, were determined by EPR spectra. In vitro release tests were performed using vertical diffusion chambers using a validated method. The quantitative determination of ketoprofen in gels, liquid and receptor medium was performed by liquid chromatography, and ethanol was quantified by gas chromatography according to validated procedures. Gels with different brands of carbomers, neutralised with trolamine or trometamol, with different contents of ketoprofen and ethanol, and with pH from 6.0 to 7.0 were studied. Results. The sol → gel transition due to the neutralisation of the carbomer did not affect the shape and parameters of the EPR spectrum of the spin probe containing a carboxyl group in the molecule (like a carbomer and ketoprofen) in contrast to the probe with an amino group. If the substance dissolved in the gels does not interact with the carbomer, then its molecules/ions rotate rapidly in the liquid medium. This facilitates the release of a such substance from carbomer-based gels. The medicinal product Nobi Gel® gel 2.5 % and Newtonian liquid were equivalent in relation to the in vitro release parameters of ketoprofen from these objects. Сarbomer-based gels, which differed significantly in terms of rheological parameters, were also found to be equivalent in terms of ketoprofen release parameters. The in vitro release of ketoprofen was affected by its concentration and ethanol content in the gel. A change in pH from 6.0 to 7.0 practically did not affect the parameters of in vitro release of ketoprofen from gels. Conclusions. The formation of a carbomer-based gel did not affect the rotational correlation time of the probe, which did not interact with the carbomer. Parameters of in vitro release of ketoprofen from the gel and Newtonian liquid differed little; these parameters were also little affected by the difference in apparent viscosity of the gels. The in vitro release of ketoprofen depended on its concentration and ethanol content

The aim. To identify the factors influencing the in vitro release of dexpanthenol (DP) from solutions and semi-solid preparations. Materials and methods. Dispersed systems containing 5.0 % DP were studied: solutions that were Newtonian liquids and semi-solid preparations (creams, gels and ointment) with non-Newtonian flow behaviour. Rheological studies were performed by rotational viscometry. In vitro release tests were performed using vertical diffusion cells. The content of DP in the receptor medium was determined by liquid chromatography. Results. It has been shown that the greatest values of release parameters of DP were characteristic of its aqueous solution; they decreased when propylene glycol (PG), macrogol 400 (M400), and poloxamer 338 (P338) were added but remained at a high enough level. The inclusion of cationic surfactant and cetostearyl alcohol (CSA) (0.5 : 4.5 % m/m) into the Newtonian liquid led to the formation of disperse system with a plastic flow behaviour and to significant decrease in the DP release. In the case of a cream containing a non-ionic surfactant and CSA, the release parameters of DP were also at a low level. The release of DP from the w/o emulsion-based ointment was minimal. Compared to DP aqueous solution, the rate of DP release from a carbomer-based gel decreased by 2.8 times; when 20 % of a mixture of PG and M400 (10 : 10 % m/m) was added to such a gel, the rate of drug release decreased by another 1.5 times. The fastest and most complete release of DP was observed in the case of the P338-based disperse system, which transformed from a Newtonian liquid into a gel at 32 °C. Conclusions. In vitro release of DP depended on the type of base; rapid and complete release of DP was characteristic of its aqueous solution, and minimal release was observed in the case of hydrophobic ointment. The use of CSA in combination with a surfactant or carbomer to create bases for semi-solid preparations with plastic flow behaviour was a considerable factor that significantly slowed down the release of DP from them. The greatest values of the release parameters of DP were observed in the case of a gel based on P338