Mestrado em Ciências Farmacêuticas
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Navegando Mestrado em Ciências Farmacêuticas por Autor "Andrade, Gracielle Ferreira"
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- ItemAvaliação antitumoral de chalconas sintéticas em sistema nanoestruturado(Universidade Federal do Espírito Santo, 2024-02-28) Sampaio, Guilherme José Schwarzt; Andrade, Gracielle Ferreira; Kitagawa, Rodrigo Rezende; https://orcid.org/0000-0002-2208-6699; Oliveira, Marcelo Antônio de; Beltrame, Flávio LuísThe difficulty faced in treating cancer has led to several researches aimed at developing systems that perform targeted drug delivery, with the aim of increasing the effectiveness of treatment and reducing adverse effects. In the present study, a series of substituted chalcones were evaluated for their cytotoxic action on gastric adenocarcinoma cells (AGS) and breast cancer cells (MCF-7) using the MTT tetrazolium method, highlighting 3-methoxychalcone, 3-chlorochalcone and 3 hydroxychalcone. Considering the physicochemical characteristics of these compounds, 3-hydroxychalcone was chosen for incorporation into mesoporous silica nanoparticles due to the presence of the hydroxyl group, which could favor the incorporation process through hydrogen interactions. The synthesis of mesoporous silica nanoparticles (MSN) and their surface modification with 3 aminopropyltriethoxylane (APTES) were carried out and, subsequently, 3 hydroxychalcone was incorporated into these materials. The mesoporous silica nanoparticles were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), elemental analysis (CHN), scanning electron microscopy (SEM), transmission electron microscopy (TEM), zeta potential and nitrogen adsorption. Furthermore, in vitro release tests were carried out to verify the release profile of 3-hydroxychalcone from mesoporous silica samples. The results obtained demonstrated that the mesoporous silica nanoparticles exhibited a gradual and prolonged release profile. In the cytotoxicity test with silica samples incorporated with 3-hydroxychalcone, important cytotoxic activity was observed (IC50 = 12.93 to 106.67 μM) against AGS and MCF-7 cells, with the MSN-CHO sample (IC50 = 12.93 to 22.30 μM) exhibited a cytotoxic effect superior to free 3-hydroxychalcone (IC50 = 47.58 to 47.97 μM). The results indicate that the nanoparticles positively influence the interaction of chalcone with tumor cells. Despite numerous published studies reporting the pharmacological potential of chalcones, few studies report the application of these compounds in drug delivery systems and the results obtained in this work indicate the great potential that these materials have for application in cancer treatment.
- ItemEntecavir: metodologia analítica por clae, estudo de estabilidade e compatibilidade IFA-excipientes(Universidade Federal do Espírito Santo, 2021-09-01) Fiorot, Ariadne Botto; Oliveira, Marcelo Antonio de; https://orcid.org/000000027842807X; http://lattes.cnpq.br/5918727154250383; https://orcid.org/0000000219221212; http://lattes.cnpq.br/4335349290318213; Nogueira, Fernando Henrique Andrade; https://orcid.org/0000-0003-0349-5814; http://lattes.cnpq.br/3818421971151621; Andrade, Gracielle Ferreira; https://orcid.org/0000-0001-9038-1254; http://lattes.cnpq.br/9137739604308170Entecavir (ETV) is an inhibitor of hepatitis B virus (HBV) DNA synthesis and has been widely prescribed in the treatment of chronic infections caused by the virus. In 2015, ETV was included on the List of Essential Medicines of the World Health Organization (WHO) and, in Brazil, it appears in the National List of Essential Medicines (RENAME) 2020. Entecavir presents polymorphism and its active crystalline form houses a molecule of water; it also presents stereoisomerism due to the presence of three chiral centers in its molecular structure. Despite the great therapeutic relevance and presence in the world market, there are still research gaps in studies of ETV degradation kinetics and its compatibility with excipients used in pharmaceutical formulations. In this work, degradation studies of entecavir in liquid medium and evaluation of drug-excipient compatibility of ETV and the inputs declared in the market formulations were carried out. The determination of ETV was performed through High Performance Liquid Chromatography (HPLC), with a method developed and validated under the following conditions: mobile phase of water and acetonitrile in the proportion 92:8, flow of 1.0 mL.min-1, temperature of 30 °C, injection of 50 μL, octadecylsilane column (RP-18) of 250 x 4.6 mm with 5 μm particles and detection at 254 nm. The forced degradation study was performed with 0.01 M HCl as the diluent of the IFA standard solution (pH 2.0) and revealed that ETV is stable when exposed to heat, UV light, metal ions and neutral, basic and acid hydrolysis; however, the drug showed vulnerability to oxidation when exposed to 3% hydrogen peroxide, with a significant reduction in the content. Kinetic degradation studies were performed under oxidative condition in two different media: pH 2.0 (with HCl 0.01 M, the validated method diluent) and pH 6.0 (with citrate buffer, present in the oral formulation of ETV). In acidic medium, extrapolated calculations demonstrated that the useful lifetime (t90) of ETV at 25 °C is 2.26 days when in contact with H2O2 3%. In a medium with citrate buffer and pH 6.0, ETV was stable and its content was not reduced under oxidative conditions, which indicates an important influence of pH on the stability of liquid formulations of entecavir. Thermal analyses by Thermogravimetry (TGA) and Differential Thermal Analysis (DTA) indicated compatibility of entecavir with the excipients microcrystalline cellulose, crospovidone, titanium dioxide, magnesium stearate, hypromellose, polyethylene glycol (macrogol), povidone and sodium citrate, which was confirmed by the HPLC technique. Compatibility tests by HPLC showed no chemical interaction of ETV with the excipients anhydrous citric acid and mannitol. Lactose monohydrate was shown to be incompatible with ETV in compatibility tests by thermal analyses and HPLC. It is recommended, for liquid formulations containing ETV: use of an antioxidant in adequate concentration, with a medium pH equal to 6.0; use of amber bottle; filling with maximum volume of the bottle and using helium gas in the agitation tank; keeping the drug away from light and heat. For solid ETV formulations, it is recommended to replace the lactose soluble diluent by the excipient mannitol, which has the same function in the formulation.
- ItemEstudo da estabilidade da melatonina e compatibilidade das formulações farmacêuticas(Universidade Federal do Espírito Santo, 2023-10-16) Balla, Débora Quintas; Oliveira, Marcelo Antonio de; https://orcid.org/000000027842807X; http://lattes.cnpq.br/5918727154250383; https://orcid.org/0009-0007-2869-1607; http://lattes.cnpq.br/4294460322479338; Andrade, Gracielle Ferreira; http://lattes.cnpq.br/9137739604308170; Castro, Whocely Victor deMelatonin (MT) is a hormone produced by the pineal gland as a product of tryptophan metabolism. Several formulations containing MT are commercially available. However, because it is considered a food supplement, there are no monographs in the Brazilian Pharmacopoeia referring to raw materials or finished products, and the requirements for registration are more flexible than those for medicines. Such a scenario reveals the need to study aspects related to the stability of this hormone and its compatibility with excipients used in the formulations. The HPLC methodology for the analysis of MT and possible degradation products was optimized and validated considering the parameters of linearity, precision, accuracy, limit of detection and quantification, selectivity, and robustness. The stability study was carried out with two active pharmaceutical ingredients from different manufacturers (APIMT1 and APIMT2). Intrinsic stability analysis showed that there was significant degradation of API under acid and basic hydrolysis, oxidation, heat exposure and photodegradation. Only in the APIMT2 samples was the formation of possible degradation products observed. A significant instability of MT under oxidation at acidic pH was observed. When evaluating the antioxidant capacity of the excipients, ascorbic acid and citric acid were the ones that showed the greatest MT protection capacity. In the evaluation of the compatibility of the formulations by Thermal Analysis, it was possible to observe and identify the melting point of MT (120.77 oC) and the characteristic event of MT degradation in all binary API-excipient mixtures (1:1), which demonstrates the compatibility. Thus, for the manufacture of MT it is important to note that the API presents degradation problems under certain stress conditions such as exposure to light, heat, oxidation, and hydrolysis; however, no excipient described for the manipulation of solid dosage forms has been shown to be incompatible. In view of the instabilities of MT under stress in liquid media, it is important to pay attention to the best packaging conditions, storage of products and pH of the formulation, and which liquid products are more susceptible to degradation compared to solid products.