Репозиторий Университета

© 2021 The aim of this work was to compare mesoporous carriers based on silica and magnesium aluminosilicate in the amorphous solid dispersion production. Darunavir has been selected as an active pharmaceutical ingredient that is classified as a Class 2 BCS substance and exists in two commercially available forms: crystalline ethanolate and amorphous. In the course of the study, the conditions for the preparation of amorphous samples with the selected carriers were evaluated within the framework of the most common methods for obtaining solid dispersions - hot-melt extrusion, solvent wetting, and spray drying. It was determined that the obtained dispersion properties almost completely repeat the properties of the corresponding carriers. The resulting dispersions were examined in a dissolution test and the best ones was used to formulate tablets, which were studied in an in vitro dissolution test with the original Prezista. The proposed tablet formulation showed improved dissolution compared to the original one. It was also found that silica supports have a greater positive contribution to darunavir dissolution - both ethanolate or amorphous forms.

© 2018 Stolichnaya Izdatelskaya Kompaniya. All rights reserved.  Aim. Investigation of comparative dissolution kinetics of generic medicinal products containing moxonidine versus reference drug. Material and methods. Objects of the research were film-coated tablets containing moxonidine (INN) in a dose 0.4 mg: a reference drug Physiotens ® and 4 generic drugs. In vitro dissolution test of moxonidine from the study drugs was performed using comparative dissolution kinetics test (CDKT). The CDKT was performed in the media with the following pH: 1.2 (1:9 mixture of 0.1 M hydrochloric acid and water), 4.5 (acetate buffer solution, prepared as per State Pharmacopoeia, XIII), and 6.8 (phosphate buffer solution, prepared as per State Pharmacopoeia, XIII). The sampling for dissolved moxonidine was performed 5, 10, 15, 20, and 30 min after the test was started. An high performance liquid chromatography method with ultraviolet detection at 220 nm was used to assay. Results. Within 15 min more that 85% of moxonidine dissolved from the reference drug and all study drugs at pH 1.2; dissolution profiles were similar without calculation of similarity factor f 2 . Similarly, at pH 4.5 dissolution profiles of study drugs #2 and #3 were similar to that of the reference drug, and the similarity factor f 2 was not calculated. However, in case of study drugs #1 and #4 significant differences were observed at a single time point (15 min), which suggests that their dissolution profiles are non-similar to that of the reference drug. Similarity factors f 2 were calculated 17.52 and 35.30, respectively (less than 50). At pH 6.8 similarity factors f 2 for all study generic drugs were also less than 50 (23.8, 49.8, 38.6, and 35.9), so their dissolution curves were non-similar to that of reference drug. Conclusion. In our study we observed difference in release in vitro of medicinal products containing moxonidines: none of the study drugs was fully similar to the reference drug in all media. The differences observed at pH 6.8 were noteworthy, where the samples had or faster kinetics (study drugs #2 and #3), or slower dissolution kinetics (test drugs #1 and #4). Observed differences in moxonidine release rate may impact absorption of active pharmaceutical ingredient into the blood following drug administration.

© 2018 BMSTU. We studied the dependence of the rate of dissolution of d-elements oxides (cobalt and copper oxides) in acidic media with EDTA additives from different factors. Increase in EDTA concentration enhances the cobalt and copper oxides dissolution, while the copper oxide dissolution is inhibited. Within the research we determined the orders by hydrogen ions and EDTA: For cobalt oxide it is 0.5 ± 0.1; for copper oxide it is nH=0,6, and by EDTA it is∼-0.6. The peculiarity of the studied kinetics in EDTA is that the rate of cobalt oxides dissolution passes through a maximum at pH =-1, for copper oxide in the presence of chelating agent EDTA the dissolution rate first decreases, and then it increases at pH from 5 to 8. The activation energy of the process is Ea (H2SO4) = = 70 kJ/mol, Ea (EDTA) = 60 kJ/mol, for copper oxide the activation energy is 73 ± 0.5 kJ/mol. The simulation of the processes showed that the surface particle, which determines the rate of dissolution is eOH+ in mineral acids, and in the chelating agent it is HY.