Flavonoids are among the most important plant metabolites. Due to their potential benefits, there is a considerable interest in this natural product. In genus Citrus, some plants have not yet been much exploited in Brazil, as in the case of grapefruit (Citrus maxima), whose main flavonoids are naringin and their aglycone naringenin. The physico-chemical characteristics are important pre-requisites of reference chemical in future studies. In this context, the objective of this study was to determine the characterization of naringin and naringenin by melting point, DSC, UV-VIS, 1H and 13C NMR, IR and MS. Results revealed that, naringin and naringenin after characterization, can be used as a chemical of reference in future studies and contribute to seeking possible technological applications.

Lipid-core polymeric nanocapsule suspensions containing adapalene and dapsone (AD-LCNC) were developed and incorporated in a Carbopol 940® hydrogel (AD-LCNC HG). A nanoemulsion (AD-NE), similarly prepared but omitting the polymer, was developed and also incorporated in a Carbopol 940 hydrogel (AD-NE HG) to evaluate the polymer effect. Physicochemical characteristics were evaluated. AD-LCNC suspensions containing 0.07% of dapsone and 0.025% of adapalene presented an average size of 194.9 ± 0.42 nm, zeta potential of -15 ± 1.2 mV and polydispersity index of 0.12 ± 0.02, using electrophoretic light scattering (n = 3). The granulometric profiles showed unimodal size distributions for AD-LCNC suspensions, demonstrating that no microscopic population is present in the formulation. No instability phenomena were observed by multiple light-scattering analysis. Photomicrographs obtained by TEM showed homogeneous- and spherical-shaped particles. The encapsulation efficiency was 99.99% for dapsone and 100% for adapalene. The pH values for AD-LCNC suspensions were 5.1 and 7.6 for AD-LCNC HG. Formulations were classified as nonirritant in the HET-CAM test. Rheological analysis demonstrated a non-Newtonian pseudoplastic profile. The in vitro skin permeation studies showed a higher amount of adapalene in epidermis (130.52 ± 25.72 ng/mg) and dermis (4.66 ± 2.5 ng/mg) for AD-NE HG. The AD-LCNC HG presented higher amount of dapsone in both the skin layers (73.91 ± 21.64 ng/mg in epidermis and 4.08 ± 0.85 ng/mg in dermis). The assay showed significant difference between AD-LCNC HG and AD-NE HG (p < 0.05), and drug was not found in the receptor medium.

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The purpose of this paper is to describe the glycosylation of ambrisentan (AMB) by cultures of Cunninghamella elegans ATCC 9245. AMB is an endothelin receptor antagonist, which is used to treat pulmonary arterial hypertension. Filamentous fungi are morphologically complex and may exhibit different forms depending on the species and the nature of the culture medium. A biotransformation study was conducted to investigate the ability of C. elegans to metabolize AMB. Parameters were optimized by testing on different culture media and concentrations, pH, drug concentration, static and shaking conditions. Ambrisentan's metabolite, obtained after 240 h of incubation as a result of glycosylation pathway, was separated by HPLC and determined by high-resolution mass spectrometry. The method showed linearity over 300-1000 μg mL −1 (r = 0.998). Accuracy, precision, robustness and stability studies agree with international guidelines. Results are consistent in accordance with the principles of green chemistry as the experimental conditions had a low environmental impact, and used little solvent.

The evaluation of drug permeation/penetration of semisolid formulations into animal skin can be useful to supplement the pharmaceutical equivalence. This paper describes the in vitro assessment of acyclovir (ACV) into porcine skin from commercial formulations with etermination of drug concentration in different layers of cutaneous tissue to correlate with effective antiviral concentration in order to improve the equivalence decision. Studies were conducted using Franz cells and porcine skin. Selected pharmaceutical creams containing ACV had identical (reference and generic) and different (similar) excipients. A software program was employed for the simulation of antiviral effectiveness in the skin. Regarding ACV skin penetration, the first batch of the generic product showed a significant difference from reference and similar products, while in the second batch all products demonstrated equivalent drug penetration in the skin. Simulation studies suggest that formulations analysed exhibit a pharmacological effect even when in contact with Herpes simplex strains of high IC 50 (inhibitory concentration required to reduce viral replication by 50%). According to results, it can be assumed that the in vitro cutaneous permeation/penetration study does not supply sensitivity information regarding small alterations of ACV semisolid formulations due to the variability inherent to the method, although it can be relevant to pharmaceutical equivalence studies in the development of semisolid products.Uniterms: Acyclovir/skin penetration/in vitro studies. Acyclovir/semisolid formulations. Acyclovir/ pharmaceutical equivalence.

Drug biotransformation studies appear as an alternative to pharmacological investigations of metabolites, development of new drug candidates with reduced investment and most efficient production. The objective of this study was to evaluate the capacity of biotransformation of Rifampicin (RIF) by the filamentous fungus Cunninghamella elegans as a microbial model of mammalian metabolism. In 120 h, C. elegans transformed the drug into the following two metabolites: rifampicin quinone and novel metabolite. The products of rifampicin formed in vitro were monitored by HPLC-PDA, being identified through UHPLC–QTOF/MS. Metabolites were characterized according to their chromatographic profile, mass fragments and UV spectral data. The major metabolic pathways of rifampicin transformed by the fungus were oxidation, demethylation and mono-oxidation. The microbial transformation of RIF showed the potential of Cunninghamella species to produce RIF metabolites. This process can be used for a cost effective method for both known and unknown metabolite production.

Naringin (NAR) and naringenin (NGE) are flavonoids with important effects, such as antioxidant, nephroprotective and anti-inflammatory action. However, factors such as poor solubility and oral bioavailability, gastrointestinal instability and extensive first pass metabolism lead to limited deliverability. As far as we know, there are no papers describing the use of combination of NAR and NGE in nanoparticles. This paper describes the development and characterization of new nanoparticles containing NAR and NGE (NAR-NGE-NPs) which were prepared by nanoprecipitation using ethanol or mixture of solvents. Size distribution of NAR-NGE-NPs demonstrated a narrow distribution (121 nm), low polydispersity (< 0.1), and encapsulation efficiencies were greater than 80%. Infrared spectroscopy analyses confirmed the structure of NAR-NGE-NPs and in transmission electron microscopy, NAR-NGE-NPs presented a spherical and regular shape. A degradation study by UV-C, NAR-NGE-NPs improved photostability and conferred protection against NAR and NGE degradation. Minimal inhibitory concentrations of NAR and NGE were evaluated, however samples did not show antimicrobial activity. In this investigation, new NAR-NGE-NPs were successfully developed by a nanoprecipitation technique, using Endragit®L100 as polymer and ethanol as solvent.

Drug biotransformation studies appear as an alternative to pharmacological studies of metabolites, development of new drug candidates with reduced investment as well as the most efficient production of chemical structures involves and drug quality control studies. A wide range of reactions in biotransformations process is catalyzed by microorganisms. Fungi can be considered as a promising source of new biotransformation reactions. The aim of this study was to evaluate the capacity of metronidazole biotransformation through the filamentous fungus Cunninghamella elegans ATCC 9245. The monitoring of metabolite formation was performed by high-performance liquid chromatography (HPLC) coupled to ultraviolet (UV) spectrophotometry. The results of the biotransformation of metronidazole showed drug consumption in culture and the formation of four new chromatographic peaks of chemical structures not elucidated. The method showed it became linear over 10-70 μg/mL (r = 0.999953). Accuracy, precision and stability studies agree with international guidelines.  Results are consistent in accordance with the principles of green chemistry as the experimental conditions had a low environmental impact, and few solvents use.