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Drug biotransformation studies emerges as an alternative to pharmacological investigations of metabolites, development of new drug candidates with reduced investment and most efficient production. The present study aims to evaluate the capacity of biotransformation of rifampicin by the filamentous fungus Aspergillus niger ATCC 9029. After incubation for 312 h, the drug was metabolized to two molecules: an isomer (m/z 455) and the rifampicin quinone (m/z 821). The monitoring of metabolite formation was performed by high-performance liquid chromatography, followed by their identification through ultra-high-performance liquid chromatography coupled to tandem mass spectrometer. In vitro antimicrobial activity of the proposed metabolites was evaluated against Staphylococus aureus microorganism, resulting in the loss of inhibitory activity when compared with the standards, with minimum inhibitory concentration of 7.5 µg/ml. The significant biotransformation power of the ATCC 9029 strain of A. niger was confirmed in this study, making this strain a candidate for pilot studies in fermentation tanks for the enzymatic metabolization of the antimicrobial rifampicin. The unprecedented result allows us to conclude that the prospect of new biotransforming strains in species of anemophilic fungi is a promising choice.

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Lipid nanoparticles (LNs) are traditional systems able to effectively increase skin hydration. However, due to its reduced viscosity, LNs suspensions are less attractive for skin administration. To overcome this disadvantage, the LN were incorporated in the semi-solid formulation is easy manipulation. This study demonstrated that it is possible to obtain novel LN-loaded fucoxanthin (LN-FUCO) for topical administration containing a combination of bacuri butter and tucumã oil prepared by high shear homogenization for improved stability. The particle size was found to be 243.0 nm and the entrapment efficiency up to 98% of FUCO was incorporated and achieved the suitability of formula. The LN-FUCO hydrogel characteristics of slight acidity, drug content near 100%, and nanometric mean size assure to this formulation high compatibility to dermal application. Photostability assay by UVA, LN-FUCO, and LN-FUCO hydrogel improved photostability and conferred greater protection against FUCO degradation. The results obtained from in vitro skin permeation studies presented a significant difference between LN-FUCO hydrogel and FUCO (p < 0.05), with no detection of the drug in the receptor medium. Therefore, high shear homogenization is demonstrated to be a simple, available, and effective method to prepare high-quality LN-FUCO hydrogel for topical application.

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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.

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ABSTRACT 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 IC50 (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.

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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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A inserção de produtos de origem vegetal em cosméticos podem melhorar as suas características. Nesse estudo, objetivou-se o desenvolvimento de formulações fotoprotetoras contendo extrato glicólico de Camelia sinensis, a avaliação da atividade fotoprotetora in vitro após a adição do extrato vegetal, bem como a avaliação das características organolépticas, a determinação do valor de pH e comportamento reológico durante 30 dias de avaliação, quando as formulações foram armazenadas nas temperaturas de 25±2°C; 5±2 °C e 40±2 °C. Após 15 dias, alterações nas características organolépticas e reológicas foram observadas nas formulações armazenadas em altas temperaturas. Em 30 dias, as formulações mantidas a temperatura ambiente e em geladeira mantiveram as características organolépticas, apesar das alterações reológicas. Observou-se uma tendência a aumento do efeito fotoprotetor com a formulação contendo FPS15 e extrato glicólico de chá verde, entretanto, não se pode atribuir melhora na estabilidade física da emulsão pela adição do extrato.

The addition of plant material to a cosmetic may improve its characteristics. The stability profile allows the performance, safety, efficacy and consumer acceptance of an emulsion to be assessed. A stability study provides information about the behavior of the product over a given time interval, under various environmental conditions. The aims of this study were to prepare sunscreen formulations containing a glycolic extract of green tea (Camellia sinensis) and to assess the photoprotective activity in vitro, the organoleptic characteristics, pH and rheological behavior over a period of 30 days, during which the formulations were stored at temperatures of 25±2°C, 5±2°C and 40±2°C. After 15 days, changes in rheological characteristics were observed in the formulation stored at the higher temperatures. After 30 days, changes were observed at other temperatures. The addition of the extract significantly changed the rheological profile of the sunscreen formulations tested. An increase in the photoprotective effect was observed when the emulsion base was compared with the emulsion containing green tea extract. However, there was no evidence of an improvement of stability when the plant extract was added to the emulsions.

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