DEFAR - Departamento de Farmácia

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Autor: search.filters.author.Barcellos, Neila Marcia SilvaTem arquivos: Sim

Resultados da Pesquisa

Agora exibindo 1 - 10 de 19
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    Effects of experimental conditions on solubility measurements for BCS classification in order to improve the biowaiver guidelines.
    (2021) Monteiro, Patrícia Fernanda; Barcellos, Neila Marcia Silva; Caldeira, Tamires Guedes; Reis, Adriana Cotta Cardoso; Ribeiro, Amanda Santos; Souza, Jacqueline de
    Among the methods described for determining the solubility, shake-flask is suitable to evaluate the equilibrium solubility according to the BCS. Nevertheless, experimental conditions related to the shake-flask method are not well described. Evaluating the effects of experimental conditions on solubility measurements by shake-flask method is important and contributes in biowaiver decision. For this work, propranolol hydrochloride and nimesulide were used as model compound of high and low solubility, respectively. Equilibrium solubility was evaluated at 37 oC, 100 rpm during 48 hours in buffer media. Effects of the rotation speed, temperature, substance in excess and aliquot withdrawn were evaluated. Small variations of temperature caused significant differences in the solubility and then this parameter must be controlled. Excess of raw material influenced the results of the nimesulide, then, little excess is recommended. Rotation speed did not cause differences in the equilibrium solubilities, but at 150 rpm the equilibrium was reached faster. Aliquot did not present significant differences, but excessive withdrawn should be avoided. Therefore, the evaluation of equilibrium solubility using shake-flask method must be performed in physiological pH conditions, 37 ± 1 oC, substance in excess 10% above saturation, 50, 100 or 150 rpm and aliquot withdrawn not more than 10% of the media volume.
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    Gliclazide : biopharmaceutics characteristics to discuss the biowaiver of immediate and extended release tablets.
    (2020) Mapa, Bruna de Carvalho; Araújo, Lorena Ulhôa; Barcellos, Neila Marcia Silva; Caldeira, Tamires Guedes; Souza, Jacqueline de
    The lists of essential medicines of the World Health Organization (WHO) and Brazil include gliclazide as an alternative to the oral antidiabetic drug of first choice, metformin, in the treatment of type 2 diabetes mellitus because of its pharmacokinetic profile and few side effects. Thus, it is also considered by WHO and the International Pharmaceutical Federation (FIP) as a drug candidate to biowaiver, which is the evaluation of how favorable the biopharmaceutics characteristics are in order to obtain waiver from the relative bioavailability/bioequivalence (RB/BE) studies to register new medicines. This paper presents a review about the solubility, permeability and dissolution of gliclazide. A critical analysis of the information allowed to identify gliclazide as a Biopharmaceutics Classification System (BCS) Class II drug. Therefore, new drugs in immediate release dosage forms will not be eligible for biowaiver. Regarding the extended release dosage forms, besides the limited solubility, no information on the comparative dissolution profile was found, which would be necessary to analyze a possible biowaiver for a smaller dosage. It can be concluded that the registration of new medicines containing gliclazide must undergo RB/BE studies, since there is not enough evidence to recommend the replacement and waiver of such studies for immediate and extended release formulations.
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    A sustainable UPLC-UV method for quantification of donepezil hydrochloride in biorelevant media applied to dissolution profile comparison.
    (2020) Campos, Débora Priscila de; Barcellos, Neila Marcia Silva; Marinho, Flávia Dias Marques; Barbosa, Guilherme Xavier; Lana, Victoria Luiza Vieira Vidigal; Souza, Jacqueline de
    Donepezil hydrochloride is one of the most prescribed anti-Alzheimer’s drugs, despite being available for more than two decades, chromatographic methods for the quantification of the drug in biorelevant media that mimics pH physiological conditions in vivo (pH 1.2, 4.5, and 6.8) are not available in the literature. These media are used in the dissolution test, an important tool, for registration and quality control of medicines. Considering the need for methods with this purpose, this work aimed to develop and validate a sustainable UPLC-UV method for quantification of donepezil hydrochloride in tablets, specifically on assay and dissolution profile, with reduced environmental impacts. The proposed method has a run time of 2 min and requires for each run, only 0.8 mL of solvents, providing excellent green analysis. The method proved to be selective, linear, precise, accurate, robust in the range of 2–14 mg/mL. Three products (reference, similar, and generic) were analyzed and showed very rapid dissolution. The average content varied from 100.2 ± 0.6% to 109.5 ± 2.1%. Using dissolution efficiency (DE), the drug release profiles were com pared in different biorelevant media.
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    The evaluation of valsartan biopharmaceutics properties.
    (2020) Castro, Lara Maria Lopes de; Souza, Jacqueline de; Caldeira, Tamires Guedes; Mapa, Bruna de Carvalho; Soares, Anna Flávia Matos; Gomes, Bruna Pegorelli; Croce, Carolina Carvalho Della; Barcellos, Neila Marcia Silva
    Background: Solubility, intestinal permeability and dissolution are the main factors that govern the rate and extent of drugs absorption and are directly related to bioavailability. Biopharmaceutics Classification System (BCS) is an important tool that uses in vitro results for comparison with bioavailability in vivo (biowaiver). Valsartan is widely used in the treatment of hypertension and shows different BCS classification in the literature (BCS class II or III). Objective: This work proposes the study of valsartan biopharmaceutics properties and its BCS classification. Method: High performance liquid chromatography (HPLC) method was developed and validated to quantify the drug in buffers pH 1.2, 4.5 and 6.8. Valsartan solubility was determined in these three different media using shake flask method and intrinsic dissolution rate. Evaluation of dissolution profile from coated tablets was conducted. Results: The low solubility (pH 1.2 and 4.5) and high solubility (pH 6.8) was observed for both solubility methods. Permeability data reported from literature showed that valsartan is a low permeability drug. Valsartan presented rapid release profile only in pH 6.8. Conclusion: We defined that valsartan is a class IV drug, in disagreement with what has been published so far. It is important to emphasize that the conditions considered here are the indicated to define the biopharmaceutics classification by regulatory agencies.
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    Patient safety in primary health care and polypharmacy : cross-sectional survey among patients with chronic diseases.
    (2019) Araújo, Lorena Ulhôa; Santos, Delba Fonseca; Bodevan, Emerson Cotta; Cruz, Hellen Lilliane da; Souza, Jacqueline de; Barcellos, Neila Marcia Silva
    Objective: to characterize and determine the polypharmacy prevalence in patients with chronic diseases and to identify the factors associated, in order to improvement of pharmaceutical care focused on patient safety. Methods: cross-sectional study included 558 patients, covered by primary health care, using a household and structured questionnaire. We analyzed the data on polypharmacy and its clinical and socioeconomic factors. Poisson regression analysis with robust variance was applied, with results expressed in prevalence ratio. Results: the results showed that polypharmacy (consumption of four or more drugs) was of 37.6%. The prevalence ratio analyses identified independent variables associated with polypharmacy: age (3.05), economic strata (0.33), way of medication acquisition through a combination of out-ofpocket and Brazilian public health system (1.44), diabetes and hypertension (2.11), comorbidities (coronary artery disease 2.26) and hospital admission (1.73). In the analyses, inappropriate medication use of the 278 patients (≥ 65 years) was associated with polypharmacy (prevalence ratio 4.04). Conclusion: polypharmacy study becomes an opportunity to guide the strategies for the patient safety to promote the medication without harm in chronic diseases.
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    Polymorphic and quantum chemistry characterization of candesartan cilexetil : importance for the correct drug classification according to Biopharmaceutics Classification System.
    (2018) Campos, Débora Priscila de; Barcellos, Neila Marcia Silva; Lima, Renata Rodrigues; Savedra, Ranylson Marcello Leal; Savedra, Melissa Fabíola Siqueira; Yoshida, Maria Irene; Mussel, Wagner da Nova; Souza, Jacqueline de
    The recommended method for the biopharmaceutical evaluation of drug solubility is the shake flask; however, there are discrepancies reported about the solubility of certain compounds measured with this method, one of them is candesartan cilexetil. The present work aimed to elucidate the solubility of candesartan cilexetil by associating others assays such as stability determination, polymorphic characterization and in silico calculations of intrinsic solubility, ionized species, and electronic structures using quantum chemistry descriptors (frontier molecular orbitals and Fukui functions). For the complete biopharmaceutical classification, we also reviewed the permeability data available. The polymorphic form used was previously identified as the form I of candesartan cilexetil. The solubility was evaluated in biorelevant media in the pH range of 1.2–6.8 at 37.0°C according to the stability previously assessed. The solubility of candesartan cilexetil is pH dependent and the dose/solubility ratios obtained demonstrated the low solubility of the prodrug. The in silico calculations supported the found results and evidenced the main groups involved in the solvation, benzimidazole, and tetrazol-biphenyl. The human absolute bioavailability reported demonstrates that candesartan cilexetil has low permeability and when associated with the low solubility allows to classify it as class 4 of the Biopharmaceutics Classification System.
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    Effect of pyridostigmine on in vivo and in vitro respiratory muscle of mdx mice.
    (2017) Amancio, Gabriela de Cássia Sousa; Guimarães, Andrea Grabe; Haikel, Dridi; Moreau, Johan; Barcellos, Neila Marcia Silva; Lacampagne, Alain; Matecki, Stefan; Cazorla, Olivier
    The current work was conducted to verify the contribution of neuromuscular transmission defects at the neuromuscular junction to Duchenne Muscular Dystrophy disease progression and respiratory dysfunction. We tested pyridostigmine and pyridostigmine encapsulated in liposomes (liposomal PYR), an acetylcholinesterase inhibitor to improve muscular contraction on respiratory muscle function in mdx mice at different ages. We evaluated in vivo with the whole-body plethysmography, the ventilatory response to hypercapnia, and measured in vitro diaphragm strength in each group. Compared to C57BL10 mice, only 17 and 22 month-old mdx presented blunted ventilatory response, under normocapnia and hypercapnia. Free pyridostigmine (1 mg/kg) was toxic to mdx mice, unlike liposomal PYR, which did not show any side effect, confirming that the encapsulation in liposomes is effective in reducing the toxic effects of this drug. Treatment with liposomal PYR, either acute or chronic, did not show any beneficial effect on respiratory function of this DMD experimental model. The encapsulation in liposomes is effective to abolish toxic effects of drugs.
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    Preclinical monitoring of drug association in experimental chemotherapy of Chagas’ disease by a new HPLC-UV method.
    (2012) Silva, Ricardo Moreira da; Oliveira, Líliam Teixeira; Barcellos, Neila Marcia Silva; Souza, Jacqueline de; Lana, Marta de
    A combination of drugs in experimental chemotherapy of Chagas’ disease may increase the effectiveness of treatment. To evaluate the possible mechanisms that influence the improvement of therapy, we investigated the pharmacokinetic interaction between benznidazole and itraconazole in a murine model treated orally with single doses of 5 mg of each compound separately or together. Blood samples from treated mice were collected at different intervals for 48 h, and a high-performance liquid chromatography (HPLC)-UV method was used to quantify both drugs in the plasma. A decrease of 1.5-fold in the maximum drug concentration in the plasma (Cmax) and an increase of 2.66-fold in the volume of distribution (V) and 7.5-fold in the elimination half-life (t1/2 ) of benznidazole when coadministered with itraconazole were observed. The parameters area under the curve (AUC0-t), area under the curve extrapolated to infinity (AUC0- ), time to maximum concentration of drug in serum (Tmax), and clearance (CL) for benznidazole were not significantly different in this therapeutic regime. None of the evaluated parameters for ITC demonstrated a significant difference between isolated and associated administration. These results suggest that the main effect of this interaction leads to accumulation of benznidazole in the biological system. This effect may contribute to the improved therapeutic efficacy of this combination of drugs, in addition to synergism of the different mechanisms of action of benznidazole and itraconazole against Trypanosoma cruzi in vivo.
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    Development and validation of an analytical method for quantification of arsenic and antimony in liposomes using inductively coupled plasma-optical emission spectrometry.
    (2013) Reis, Priscila Gomes dos; Abreu, Adriana Trópia de; Guimarães, Andrea Grabe; Teixeira, Mônica Cristina; Souza, Jacqueline de; Barcellos, Neila Marcia Silva
    Arsenic and antimony compounds are used to treat endemic diseases, such as cancer, leishmaniasis, and schistosomiasis, in spite of their toxicity. Several studies seeking the development and characterization of nanocarrier systems such as liposomes are being carried out with the aim of developing new drug delivery systems and minimizing the toxicity of these drugs. However, the lack of reference methods to quantify these semimetals within a liposomal matrix hinders the QC of these formulations. Therefore, the validation of an analytical method for arsenic and antimony quantification in liposomal matrix by inductively coupled plasma-optical emission spectrometry is presented here. The linearity, specificity, LOD, LOQ, accuracy, and precision were determined according to the International Conference on Harmonization norms and the Brazilian Health Surveillance Agency (Resolution 899). The LOD values were 0.02 and 0.06 mg/L for antimony and arsenic, respectively. The LOQ for both was 3.0 mg/L, with an adequate accuracy within 98.26 and 101.32% for different levels of antimony and 99.98 and 100.36% for arsenic. Precision (CV) was lower than 5.0%. The developed and validated method was shown to be reproducible for quantification of arsenic and antimony in liposome pharmaceutical dosage forms.
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    Long-lasting cardiovascular effects of liposomes-entrapped angiotensin-(1-7) at the rostral ventrolateral medulla.
    (2001) Barcellos, Neila Marcia Silva; Frezard, Frederic Jean Georges; Caligiorne, Sordaini Maria; Santos, Robson Augusto Souza dos
    The aim of this work was to evaluate the potential of liposomes as a tool for the sustained release of the short half-life peptides of the renin-angiotensin system in a specific site of the brain. Angiotensin (Ang)-(1-7) was selected for this study because of its known cardiovascular effects at the level of the rostral ventrolateral medulla (RVLM) and because of the considerable interests in elucidating its physiopathological role as a neuromodulator. Ang-(1-7)– containing liposomes (LAng) were microinjected unilaterally in the RVLM of Wistar rats, and the effects on blood pressure (MAP) and heart rate were evaluated by telemetry. Empty liposomes (Lemp) were used as control. LAng elicited a significant pressor effect during daytime and bradycardia during nighttime that lasted for 5 and 3 days, respectively. These cardiovascular effects resulted in a significant attenuation of the circadian variations of MAP and heart rate. In the case of MAP, a significant inversion of the circadian rhythm was observed on day 2 after LAng microinjection. None of these effects were observed following microinjection of Lemp. Using this novel technique, it was possible to establish, in chronic conditions, the pressor effect of Ang-(1-7) at the RVLM. Moreover, our data unmasks a new physiological role for Ang-(1-7) at the level of the RVLM: modulation of the circadian rhythms of MAP and heart rate.