The sodium 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydropyrimidine-4-olate quantitative content determination in a standard sample

Introduction. The standard samples (SS) use is a necessary condition for the medicines' quality control implementation. Their development is an urgent problem for the pharmaceutical industry, especially for new biologically active compounds that can be further used as pharmaceuticals.Aim. This work aim is to establish the 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydro pyrimidone-4-olate sodium quantitative content, for which anti-inflammatory and analgesic activity was previously proven, in a standard sample.Materials and methods. This work aim is to establish the 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydro pyrimidone-4-olate sodium quantitative content, for which anti-inflammatory and analgesic activity was previously proven, in a standard sample. The main method for establishing a substance quantitative content in the SS is the material balance method. The water determination was carried out according to K. Fisher's method (semimicro method). Sulphated ash was determined according to the XIV edition Russian Federation State Pharmacopoeia General Pharmacopoeia Monograph "Sulphated ash". Related impurities and their content were assessed using the HPLC method on a Flexar liquid chromatograph equipped with a diode array detector (Perkin Elmer, USA). The residual solvents' determination was carried out by the headspace method using a gas chromatograph GC-2010Plus Shimadzu with a flame ionization detector. As an additional method for establishing the main component quantitative content, acidimetric titration with the equivalence point potentiometric indication was carried out.Results and discussion. The percentage was determined for the following indicators: water, residual organic solvents, related impurities, sulphated ash. Using the material balance method, it was found that the 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydropyrimidin-4-olate sodium percentage in a standard sample is 96.01 ± 0.50 %. It was found by acidimetric titration that the 5-butyl-1,2-diphenyl-6-oxo 1,6-dihydropyrimidin- 4-olate sodium quantitative content in SS is 95.12 ± 0.02 %. The difference in the certified value can be explained by the fact that during titration, the SS aciform is released, which precipitates in an aqueous medium and contributes to a shift in the equilibrium and pH value. Consequently, the equivalence point is reached somewhat earlier. However, the data are practically comparable, but it is necessary to use the value obtained by the material balance method.Conclusion. A standard sample certification parameters were determined: water content, residual organic solvents, sulphated ash, related impurities. The main component quantitative content was determined using the material balance method and titrimetry (acidimetry with the equivalence point potentiometric indication).

Supercritical CO2 Extraction of Organic Solvents from Flunisolide and Fluticasone Propionate

In this work, Class 2 and Class 3 solvents contained in two corticosteroids, flunisolide (Fluni) and fluticasone propionate (Fluti), were reduced to a few ppm by supercritical CO2 extraction. The process was carried out at pressures from 80 to 200 bar, temperatures of 40 °C and 80 °C, and at a fixed CO2 flow rate of 0.7 kg/h. The results demonstrated that CO2 density is the key parameter influencing the extraction kinetics and the solvent final residue. In particular, in the range investigated, optimal pressure and temperature conditions for the extraction of residual organic solvents were found working at 200 bar and 40 °C, which corresponds to a CO2 density of 0.840 g/cm3. Operating in this way, total organic solvent residues were reduced from 13,671 ppm and 326 ppm to 12 ppm and 10 ppm for Fluni and Fluti, respectively.

Preserving the Integrity of Liposomes Prepared by Ethanol Injection upon Freeze-Drying: Insights from Combined Molecular Dynamics Simulations and Experimental Data

The freeze-drying of complex formulations, such as liposomes, is challenging, particularly if dispersions contain residual organic solvents. This work aimed to investigate the effects of possible protectants, namely sucrose, trehalose and/or poly(vinyl pyrrolidone) (PVP), on the main features of the dried product using a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-based liposomal dispersion prepared by ethanol injection and containing ethanol up to 6%, as a model. The interactions among vesicles and protectants were preliminary screened by Molecular Dynamics (MD) simulations, which have been proved useful in rationalizing the selection of protectant(s). The freeze-drying protocol was based on calorimetric results. Overall data suggested a stronger cryo-protectant effect of trehalose, compared with sucrose, due to stronger interactions with the DPPC bilayer and the formation of highly ordered clusters around the lipids. The effect further improved in the presence of PVP. Differently from the other tested protectants, the selected trehalose/PVP combination allows to preserve liposome size, even in the presence of 6% ethanol, as demonstrated by Nanoparticle Tracking Analysis (NTA). Nevertheless, it should be also underlined that cakes blew out at an ethanol concentration higher than 1% v/v, probably due to the poor cohesion within the cake and solvent vapour pressure upon sublimation.