Development and <i>in vitro/in vivo</i> evaluation of a novel benznidazole liquid dosage form using a quality‐by‐design approach

Souza, Higo Fernando Santos; Real, Daniel Andrés; Leonardi, Darío; Rocha, Sandra Carla; Alonso, Victoria Lucía; Serra, Esteban; Silber, Ariel Mariano; Salomón, Claudio J.

doi:10.1111/tmi.12980

Cited by 16 publications

(10 citation statements)

References 36 publications

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“…Besides solid oral dosage form development and optimization, DoE is vastly used in several other pharmaceutical formulation techniques, such as hot melt granulation (69,70), liquid dosage forms (71,72), liposome formulations (73,74) and nanostructured lipid carriers (75).…”

Section: Table I Most Frequently Used Methods In Experimental Designsmentioning

confidence: 99%

Quality-by-design in pharmaceutical development: From current perspectives to practical applications

et al. 2021

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Current pharmaceutical research directions tend to follow a systematic approach in the field of applied research and development. The concept of quality-by-design (QbD) has been the focus of the current progress of pharmaceutical sciences. It is based on, but not limited, to risk assessment, design of experiments and other computational methods and process analytical technology. These tools offer a well-organized methodology, both to identify and analyse the hazards that should be handled as critical, and are therefore applicable in the control strategy. Once implemented, the QbD approach will augment the comprehension of experts concerning the developed analytical technique or manufacturing process. The main activities are oriented towards the identification of the quality target product profiles, along with the critical quality attributes, the risk management of these and their analysis through in silico aided methods. This review aims to offer an overview of the current standpoints and general applications of QbD methods in pharmaceutical development.

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Section: Table I Most Frequently Used Methods In Experimental Designsmentioning

confidence: 99%

Quality-by-design in pharmaceutical development: From current perspectives to practical applications

et al. 2021

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“…Isso poderia resultar em uma melhor absorção e aumento da biodisponibilidade, melhorando assim o comportamento biofarmacêutico do BZ. Souza et al (2017), desenvolveram soluções de BZ sem álcool usando PEG 400, propilenoglicol (PPG) e água como solventes selecionados. Os resultados obtidos no estudo revelam uma relação direta entre a concentração de PEG 400 e a solubilidade de BZ.…”

Section: Desenvolvimento De Novas Alternativas Terapêuticasunclassified

“…Os excipientes incluídos na formulação final cobriram efetivamente o sabor amargo do fármaco. Já os estudos in vivo confirmaram a adequação da formulação desenvolvida de BZ para reduzir a parasitemia e a mortalidade, particularmente na dose de 40 mg/kg/dia (Souza et al, 2017).…”

Section: Desenvolvimento De Novas Alternativas Terapêuticasunclassified

Doenças negligenciadas e indústria farmacêutica: o caso da Doença de Chagas

Silva

Dantas

Silva

et al. 2021

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O desenvolvimento de novos fármacos, no contexto das Doenças Tropicais Negligenciadas (DTNs), permanece como um grande desafio. Dentre as DTNs, destaca-se a Doença de Chagas (DC), a qual possui elevada morbimortalidade. Assim, este estudo objetiva resgatar informações acerca do cenário atual, bem como novas estratégias e inovações no tratamento farmacológico da DC. Para tal, foi realizada uma revisão narrativa, em que foram selecionados artigos no PubMed, SciELO e LILACS, no período entre 2015 e 2020. Buscando avaliar a relevância no meio acadêmico, comparou-se o número de publicações no SciELO entre 1950 e 2019, sobre DC, diabetes mellitus e câncer. Também se buscou informações sobre ensaios clínicos no site ClinicalTrials.gov. Nos últimos 20 anos, o número de publicações sobre a DC no SciELO foi bastante inferior se comparado com diabetes mellitus e câncer. Ademais, apenas dois medicamentos estão disponíveis, sendo eles benznidazol e nifurtimox, os quais possuem limitações como a quantidade de efeitos adversos. Por isso, novas opções terapêuticas (grânulos, sistemas multiparticulados, etc) têm sido estudadas, principalmente no caso do benznidazol, tendo demonstrado resultados promissores quanto à otimização de toxicidade, absorção e biodisponibilidade, por exemplo. Quanto aos ensaios clínicos, foi encontrado um total de sete estudos, os quais investigam cinco compostos para o tratamento da DC. Somente um dos compostos não tem uso clínico já registrado, o selênio, o que sugere uma deficiência na busca por novos candidatos à fármacos. Tais informações reforçam, portanto, o caráter negligenciado da DC, bem como enfatizam a importância de pesquisar novas terapias para esta parasitose.

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“…BZ is the preferred drug for the treatment of acute ChD. In this sense, it is worthy of note that several BZ delivery platforms and formulations are been assayed in pre-clinical studies (Scalise et al, 2016;Santos Souza et al, 2017;García et al, 2018) and a pediatric formulation of BZ is available since 2011 2 , improving dosing accuracy, safety, and adherence to treatment. Both BZ and NFX are pro-drugs that are cleaved to their active form in the parasite by nitroreductase type I (NTR-I) (Hall et al, 2011;Hall and Wilkinson, 2012).…”

Section: Drugs-derived Oxidative Stressmentioning

confidence: 99%

Redox Balance Keepers and Possible Cell Functions Managed by Redox Homeostasis in Trypanosoma cruzi

Mesías

Garg

Zago

2019

Front. Cell. Infect. Microbiol.

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The toxicity of oxygen and nitrogen reactive species appears to be merely the tip of the iceberg in the world of redox homeostasis. Now, oxidative stress can be seen as a two-sided process; at high concentrations, it causes damage to biomolecules, and thus, trypanosomes have evolved a strong antioxidant defense system to cope with these stressors. At low concentrations, oxidants are essential for cell signaling, and in fact, the oxidants/antioxidants balance may be able to trigger different cell fates. In this comprehensive review, we discuss the current knowledge of the oxidant environment experienced by T. cruzi along the different phases of its life cycle, and the molecular tools exploited by this pathogen to deal with oxidative stress, for better or worse. Further, we discuss the possible redox-regulated processes that could be governed by this oxidative context. Most of the current research has addressed the importance of the trypanosomes' antioxidant network based on its detox activity of harmful species; however, new efforts are necessary to highlight other functions of this network and the mechanisms underlying the fine regulation of the defense machinery, as this represents a master key to hinder crucial pathogen functions. Understanding the relevance of this balance keeper program in parasite biology will give us new perspectives to delineate improved treatment strategies.

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Development and in vitro/in vivo evaluation of a novel benznidazole liquid dosage form using a quality‐by‐design approach

Cited by 16 publications

References 36 publications

Quality-by-design in pharmaceutical development: From current perspectives to practical applications

Quality-by-design in pharmaceutical development: From current perspectives to practical applications

Doenças negligenciadas e indústria farmacêutica: o caso da Doença de Chagas

Redox Balance Keepers and Possible Cell Functions Managed by Redox Homeostasis in Trypanosoma cruzi

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