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The growing interest in anticancer hybrids in the last few years has resulted in a great number of reports on hybrid design, synthesis and bioevaluation. Many novel multi-target-directed drug candidates were synthesized, and their biological activities were evaluated. For the design of anticancer hybrid compounds, the molecules of stilbenes, aromatic quinones, and heterocycles (benzimidazole, imidazole, pyrimidine, pyridine, pyrazole, quinoline, quinazoline) were applied. A distinct group of hybrids comprises the molecules built with natural compounds: Resveratrol, curcumin, coumarin, and oleanolic acid. In this review, we present the studies on bioactive hybrid molecules of a well-known tubulin polymerization inhibitor, combretastatin A-4 and its analogs with other pharmacologically active entities. The mechanism of anticancer activity of selected hybrids is discussed considering the structure-activity relationship.

Ginkgo biloba extract is a popular ingredient in pharmaceutical formulations. The level of bioactive compounds determines final antioxidant activity of an extract and its therapeutic efficiency. The aim of the project was to assess phytopharmaceuticals containing Ginkgo extracts in terms of their chemical characteristic and antioxidant activity using selected chemometric methods. The aim of the study was also to investigate whether the antioxidant activity of phytopharmaceuticals can be successfully predicted based on their chromatograms. Total polyphenol content and antioxidant activity of methanolic Ginkgo extracts were determined using a spectrophotometric technique. Comparative chemometric analysis of investigated pharmaceutical formulations was carried out using hierarchical and non-hierarchical segmentation algorithms. Samples of herbal drug products were clearly separated from samples of dietary supplements. A tree regression method was used to predict the antioxidant activity of pharmaceuticals based on the chromatographic description. The correlations between the predicted (by regression model) and experimental values of IC50 for training and testing subset were 0.960 and 0.949, respectively. The chemometric techniques, combined with instrumental analysis, could improve and simplify the quality control methods of herbal products. The antioxidant activity, predicted on the basis of chromatograms, may be one of measures of final product quality.

Development and optimization of the activated charcoal suspension composition based on a mixture design approachIn this study, a new drug product containing activated charcoal was designed and developed. The excipient levels in the pharmaceutical formulation were optimized using a mixture design approach. The adsorption power of the activated charcoal suspension was selected as the critical quality attribute influencing the efficacy of medical treatment. Significant prognostic models (p < 0.05) were obtained to describe in detail the interrelations between excipient levels and the adsorption power of the formulation. Liquid flavour had a critical impact on the adsorption power of the suspension. Formulations containing the largest amount of liquid flavour showed the lowest adsorption power. Sorbitol was not adsorbed onto activated charcoal so strongly as liquid flavour. A slight increase in the content of carboxymethylcellulose sodium led to a marked decrease in adsorption power. The obtained mathematical models and response surface allowed selection of the optimal composition of excipients in a final drug product.Keywords: activated charcoal, adsorption power, phenazone, experimental design, Quality by Design concept The Quality by Design concept is an essential part of the modern approach to pharmaceutical quality. It involves designing and developing formulations and manufacturing processes to ensure predefined drug product quality (1). Due to the current trend of being Quality by Design compliant, the use of experimental designs in pharmaceutical sciences is increasing (2, 3). This strategy can shorten a drug development phase and reduce the overall experimental work and costs (4, 5). Furthermore, the use of experimental design techniques enables better understanding of the effect of material attributes and process factors on the final drug product quality (5).This paper focuses on the application of experimental design in the development and optimization of a new drug product containing activated charcoal. The composition of excipients in the formulation was optimized using a mixture design approach according to the ICH Q8 guidelines (6). The adsorption power of the activated charcoal suspension was considered as the critical quality attribute to be studied in order to establish the optimal