Preparation and Characterization of Poloxamer 407 Solid Dispersions as an Alternative Strategy to Improve Benznidazole Bioperformance

Simonazzi, Analía; Davies, Carolina; Cid, Alicia Graciela; Gonzo, Elio Emilio; Parada, Luis Antonio; Bermúdez, José Marı́a Ancochea

doi:10.1016/j.xphs.2018.06.027

Cited by 29 publications

(15 citation statements)

References 28 publications

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“…This high melting point also suggests its highly crystalline nature. Likewise, the thermogram of hygroscopic PVP K30 showed a wide endothermic peak at 150.57 °C due to the dehydration of polymer, while poloxamer 407 had a sharp peak at 55.55 °C; these are comparable to the values reported in the literature [24,33]. The characteristic endothermic peaks of the drug and each excipient were observed in PM, implying that the crystal nature of the drug was retained in the physical mixture.…”

Section: Resultssupporting

confidence: 82%

Development of a Ternary Solid Dispersion Formulation of LW6 to Improve the In Vivo Activity as a BCRP Inhibitor: Preparation and In Vitro/In Vivo Characterization

et al. 2019

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LW6 (3-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-4-hydroxy-benzoic acid methyl ester) is a potent inhibitor of drug efflux by the breast cancer resistance protein (BCRP). However, its poor aqueous solubility leads to low bioavailability, which currently limits in vivo applications. Therefore, the present study aimed to develop ternary solid dispersion (SD) formulations in order to enhance the aqueous solubility and dissolution rate of LW6. Various SDs of LW6 were prepared using a solvent evaporation method with different drug/excipient ratios. The solubility and dissolution profiles of LW6 in different SDs were examined, and F8-SD which is composed of LW6, poloxamer 407, and povidone K30 at a weight ratio of 1:5:8 was selected as the optimal SD. The structural characteristics of F8-SD were also examined using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM). In the acidic to neutral pH range, F8-SD achieved rapid dissolution with a drug release of 76–81% within 20 min, while the dissolution of pure LW6 was negligible. The XRPD patterns indicated that F8-SD probably enhanced the solubility and dissolution of LW6 by changing the drug crystallinity to an amorphous state, in addition to the solubilizing effect of the hydrophilic carriers. Furthermore, F8-SD significantly improved the oral bioavailability of topotecan, which is a BCRP substrate, in rats. The systemic exposure of topotecan was enhanced approximately 10-fold by the concurrent use of F8-SD. In conclusion, the ternary SD formulation of LW6 with povidone K30 and poloxamer 407 appeared to be effective at improving the dissolution and in vivo effects of LW6 as a BCRP inhibitor.

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Section: Resultssupporting

confidence: 82%

Development of a Ternary Solid Dispersion Formulation of LW6 to Improve the In Vivo Activity as a BCRP Inhibitor: Preparation and In Vitro/In Vivo Characterization

et al. 2019

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“…Chagas disease is an infection that affects around eight million people around the world, mainly in Latin America, which is treated with nifurtimox and benznidazole (BNZ). Although the latter is preferable because of fewer adverse effects than the former, it has low solubility, which limits its effectiveness in treating the disease [ 25 ].…”

Section: In Vitro Study Of Solid Dispersions In Polymeric Matricesmentioning

confidence: 99%

“…To potentiate the effect of the same drug, Simonazzi et al [ 25 ] prepared a BNZ-containing SD using Poloxamer 407 (P407) as polymer, whose in vitro activity was tested by the MTT method against T. cruzi (Tulahuén lineage) in the epimastigote phase at a concentration of 4 × 107 cells/mL. SD showed higher antiparasitic activity (IC50 of 21.68 ± 1.6 µM) than BNZ alone (32.47 ± 4.9 µM), likely because P407 significantly improved BNZ solubility and consequently increased the rate of its release compared to the other preparations.…”

Section: In Vitro Study Of Solid Dispersions In Polymeric Matricesmentioning

confidence: 99%

Therapeutic Applications of Solid Dispersions for Drugs and New Molecules: In Vitro and In Vivo Activities

et al. 2020

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This review aims to provide an overview of studies that address the use, in therapeutic applications, of solid dispersions (SDs) with biological activities in vitro and/or in vivo mainly made up of polymeric matrices, as well as to evaluate the bioactive activity of their constituents. This bibliographic survey shows that the development of solid dispersions provides benefits in the physicochemical properties of bioactive compounds, which lead to an increase in their biological potential. However, despite the reports found on solid dispersions, there is still a need for biological assay-based studies, mainly in vivo, to assist in the investigation and to devise new applications. Therefore, studies based on such an approach are of great importance to enhance and extend the use of solid dispersions in the most diverse therapeutic applications.

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“…Por outro lado, o excesso de fármaco pode precipitar no fluido gastrointestinal em partículas muito finamente divididas. Estas características frequentemente resultam em absorção de fármaco notavelmente melhorada de um SD em comparação com um comprimido convencional ou formulação de cápsula (Simonazzi et al, 2018). Simonazzi et al (2018), realizaram um estudo sobre essas dispersões sólidas usando Poloxamer 407 como transportador, o SD manteve a eficácia do BZ em relação à sua atividade antitripanocida.…”

Section: Desenvolvimento De Novas Alternativas Terapêuticasunclassified

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

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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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Preparation and Characterization of Poloxamer 407 Solid Dispersions as an Alternative Strategy to Improve Benznidazole Bioperformance

Cited by 29 publications

References 28 publications

Development of a Ternary Solid Dispersion Formulation of LW6 to Improve the In Vivo Activity as a BCRP Inhibitor: Preparation and In Vitro/In Vivo Characterization

Development of a Ternary Solid Dispersion Formulation of LW6 to Improve the In Vivo Activity as a BCRP Inhibitor: Preparation and In Vitro/In Vivo Characterization

Therapeutic Applications of Solid Dispersions for Drugs and New Molecules: In Vitro and In Vivo Activities

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

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