Vol 52, No 11 (2019)

The concept of enhancers or transcutaneous conductors and their classification and mechanism of action are discussed. Special attention is paid to transcutol, a conductor with pronounced solubilizing and penetrating properties that facilitates the accumulation of locally applied medicines in the skin lipid layer without perturbing its structure. The transcutaneous action effectiveness of chemical enhancers is shown to depend on not only the structure and concentration but also the physicochemical characteristics of the penetrating drugs. Diffusional transport in the stratum corneum and the ability to monitor the occurring processes can be used to optimize the design of drugs for transcutaneous targeted delivery.

A polymer dosage form of etoposide (PFE) was obtained as submicron particles based on the copolymer of lactic and glycolic acids (PLGA). Pharmacokinetics and biodistributions of etoposide in rat blood and organs after a single i.p. injection of the polymeric form and etoposide drug substance at doses of 10 mg/kg (of active ingredient) were compared and showed that absorption and elimination of etoposide from rat organs slowed if the PFE was used. The increases of T_1/2 and MRT and decreases of K_el, C_max/AUC_{(0 – 48)}, and Cl were indicative of this. Liver and lungs had the greatest tissue availability (f_t) for the PFE. Etoposide accumulation in tumor tissue was studied after a single i.p. injection of PFE and etoposide drug substance at doses of 25 mg/kg to mice with grafted Ca755 murine breast adenocarcinoma. The etoposide distribution coefficient between blood and tumor tissue after 1 and 24 h was greater for the PFE, indicating the accumulation of etoposide in tumor tissue was greater if the PFE was used.

The anti-inflammatory activity of tyrosol and 12 structural analogs including 3 new compounds was determined. Several structure-activity (anti-inflammatory) relationships were found. Adding a tert-butyl substituent to the aromatic ring and increasing the length of the alkyl chain decreased the anti-inflammatory activity. Pronounced antiulcer activity was found for p-tyrosol.

(E)-3-(3-(Allyloxy)-2-methoxyphenyl)-1-(2,4,6-trimethoxyphenyl)prop-2-en-1-one displayed potent antiproliferative activity against the PC-3 cell line. For colony assay, it can inhibit the colony formation at a concentration of 10 μM. Morphological changes of PC-3 cells were determined using DAPI (4′,6-diamidino-2-phenylindole) staining and chromatin condensation. Treatment with this compound at 10 μM induced apoptosis from 2.0% to 30.4% compared with control according to flow cytometry analysis. It also induced the downregulation of apoptosis-related markers Bcl-2 and XIAP (X-linked inhibitor of apoptosis protein). However, treatment with NAC (N-acetyl-L-cysteine) almost completely attenuated chalcone-induced cell inhibition and cell apoptosis in PC-3 cells.

Rapid and correct identification of microorganisms is an essential part of pharmaceutical analysis. Several phenotypic, genotypic, and proteotypic methods, each of which has its own advantages and limitations, are currently used to identify microorganisms. The aim of the present work was to reveal features and validate the operation of a Vitek 2 Compact 30 bacteriological analyzer (bioMerieux, France), which was based on determining the biochemical properties of microorganisms. The applicability of this method was determined using accuracy, precision, and robustness. Correct results were found in 86% of 396 cases. Results obtained under repeatability and intermediate precision conditions showed no differences. Approaches to molecular and genetic identification of microorganisms isolated from preparations in addition to automated biochemical identification were discussed.

An UV-spectrophotometric method for simultaneous determination of amlodipine and captopril has been developed and validated. Simultaneous equation method is applied for the quantification of both drugs, which is based upon the measurement of absorbance at two wavelengths, λ_max = 236 and 213 nm for amlodipine and captopril, respectively, in 0.1 N HCl solutions. The calibration curves for amlodipine and captopril are linear in concentration ranges of 0.195 – 100 and 0.39 – 100 μg/mL, respectively. Accuracy of the method is 98 and 99% for amlodipine and captopril, respectively. The inter-day precision for amlodipine and captopril in terms of RSD is 10 and 8%, while the intra-day RSD is 6 and 9%, respectively. Sensitivity of the method in term of the limit of detection for amlodipine and captopril is 0.195 and 0.39 μg, respectively. The method gives 98% reproducible results.

Series of semi-synthetic polyene macrolide antibiotics (PMAs) that were prepared by chemical modification in original research by the authors are reviewed. Chemical modification, in particular phosphorylation, was shown to produce highly efficacious PMAs with low toxicities and extended spectra of biological activity. The prospects of using liposomal and nano-derivatives of these antifungal antibiotics are discussed. Crucial issues related to the resistance of pathogenic fungi and the expanding distribution of invasive mycoses are identified. Semi-synthetic PMAs are shown to be highly effective at preventing and treating invasive mycoses and opportunistic fungal infections occurring in AIDS patients. Special attention is paid to structure—activity relationships for the semi-synthetic PMAs. Possible mechanisms of action of these compounds on pathogenic fungi are discussed. An automated intellectual information system was developed for selecting the optimal conditions for development, synthesis, and application in medical practice of new PMAs.

Methods for selective chemical modification of the antitumor antibiotic olivomycin A(OA) were developed at GINA. The compound olivamide with advantages over starting OA was selected from series of OA analogs. The goal of the present work was to develop a dosage form of the antitumor semi-synthetic antibiotic olivamide that guaranteed the stability and high specific activity of olivamide drug substance and was designed for further comprehensive preclinical studies.

General approaches to the elaboration of pharmacopoeial quality standards for medicinal products that are based on good pharmacopoeial practice (GPhP) rules of domestic and leading foreign pharmacopoeias are presented.