Scielo RSS <![CDATA[Brazilian Journal of Pharmaceutical Sciences]]> vol. 53 num. 4 lang. es <![CDATA[SciELO Logo]]> <![CDATA[The mechanism of drug interactions of a selected antiarrhythmic drug with metformin, in different animal models]]> ABSTRACT This study was carried out to understand the influence of a selected antiarrhythmic drug on the pharmacodynamics and pharmacokinetics of an antidiabetic drug in animal models. Pharmacodynamic and pharmacokinetic responses were determined by measurements of blood glucose and serum insulin and serum metformin to drug interactions between disopyramide and metformin. Single dose and multi dose studies showed that the maximum blood glucose reductions in normal and diabetic rats were at the 6th hour, and in rabbits at the 3rd hour. Glucose-insulin homeostasis was evaluated to assess the safety and effectiveness of the combination. There was a marginal increase in the pharmacokinetic parameters of metformin with multiple dose treatments of disopyramide but no significant changes in kinetic parameters between single and multiple dose studies, compared to metformine alone. There may be a possibility of disopyramide and metformin interaction at the excretion stage, or an additive pharmacodynamic action. This study validates the drug interaction in two dissimilar species, which indicates more probability of its occurrence in humans. <![CDATA[Evaluation of antimicrobial, cytotoxic and chemopreventive activities of carvone and its derivatives]]> ABSTRACT Considering the reported activity of carvone in the literature, this study aimed to evaluate the antimicrobial, cytotoxic and chemopreventive activities of (+)- and (-)-carvone, (+)- and (-)- hydroxydihydrocarvone and α,β-epoxycarvone. (+)-Hydroxydihydrocarvone (HC+), (-)-hydroxydihydrocarvone (HC-) and α,β-epoxycarvone (EP) were obtained by synthesis using (+)-carvone (C+) or (-)-carvone (C-) as precursors. The antifungal activity (MIC and MFC) were evaluated against Candida parapsilosis, C. tropicalis, C. krusei and C. albicans and the antibacterial activity (MIC and MBC) against Escherichia coli and Staphylococcus aureus. The cytotoxicity assays were performed with human cancer cell lines HepG-2 and SiHa and the normal strain MRC-5 through sulphorrodamine B assay. Chemoprevention was evaluated through quinone reductase assay. Our results showed no cytotoxicity on tumor and normal cell lines and no induction of the quinone reductase enzyme. C- and HC- presented activity against E. coli. All compounds presented weak antifungal activity against C. tropicalis and C. parapsilosis. EP and C+ showed moderate activity against C. krusei. Results suggest the potential use of carvones and its derivatives as antifungal agents against Candida yeasts. The absence of cytotoxicity in cell lines indicates safety in the use of these compounds. <![CDATA[Molecular docking, synthesis and <em>in vitro</em> antimalarial evaluation of certain novel curcumin analogues]]> ABSTRACT The receptor protein PfATP6 has been identified as the common target of artemisinin and curcumin. The work was initiated to assess the antimalarial activity of six curcumin derivatives based on their binding affinities and correlating the in silico docking outcome with in vitro antimalarial screening results. A ligand library of thirty two Knoevenagel condensates of curcumin were designed and docked against PfATP6 protein and six compounds with the best binding scores were synthesized and screened for their antimalarial activity against the sensitive 3D7 strain of Plasmodium falciparum. ADME/Tox, pharmacokinetic and pharmacodynamic profiles of the designed compounds were analyzed and reported. 4-FB was found to have similar binding energy to the standard artemisinin (-6.75 and -6.73 respectively) while 4-MB, 3-HB, 2-HB, B, 4-NB displayed better binding energy than curcumin (-5.95, -5.89, -5.68, -5.35, -5.29 and -5.25 respectively). At a dose of 50 µg/mL all the six compounds showed 100% schizont inhibition while at 5µg/ml, five showed more than 75% inhibition and better results than curcumin. 4-FB showed the best activity with 97.8% schizonticidal activity. The in vitro results superimpose the results obtained from the in silico study thereby encouraging development of promising curcumin leads in the battle against malaria. <![CDATA[Prednisone raw material characterization and formulation development]]> ABSTRACT Solid dosage forms for oral use, particularly tablets, are the most highly used dosage forms in therapy because they are easily administered, have high productivity and relatively low cost and provide a more stable drug to form a semi-solid net. Numerous parameters influence the quality of the final dosage form. In this study, the dissolution profile of 20-mg prednisone tablets bioequivalent to the reference product and three test formulations were evaluated using stability testing. During the study, prednisone tablets and the active pharmaceutical ingredient (API) prednisone from two different manufacturers were characterized with respect to their physical and physicochemical properties. The results showed that the dissolution profiles of the test batches and the reference product did not retain pharmaceutical equivalence throughout all the stability study. Notably, both samples of API prednisone were of the same crystal form, and any phase transition that occurred during the study could not be attributed to dissolution variation during stability.