Development of dissolution method for benznidazole tablets

The aim of this work was the development of a dissolution method for benznidazole (BNZ) tablets. Three different types of dissolution media, two stirring speeds and apparatus 2 (paddle) were used. The accomplishment of the drug dissolution profiles was compared through the dissolution efficiency. The assay was performed by spectrophotometry at 324 nm. The better conditions were: sodium chloridehydrochloride acid buffer pH 1.2 with stirring speed of 75 rpm, volume of 900 mL and paddle as apparatus. Ahead of the results it can be concluded that the method developed consists in an efficient alternative for assays of dissolution for benznidazole tablets

Određivanje fizikalno-kemijskih svojstava, stabilnosti i citotoksičnosti plavog bojila dobivenog iz ploda jague (Genipa americana L.)

Research background. The current commercial scenario indicates an increase in the demand for natural dyes. Compared to synthetic dyes, natural ones have the advantage of being sustainable, making them of great interest for the food and cosmetic industries. The development of new natural dyes is necessary, as well as the carrying out of complementary research regarding the existing ones. Experimental approach. The present study aims to characterize the physicochemical and biological characteristics of the dye obtained from dehydrated endocarp of the genipap (Genipa americana) fruit, as well as perform the relevant stability and cytotoxicity tests. The chemical characterization was performed by HPLC-MS/MS analyses. The stability studies were carried out by spectrophotometry and cytotoxicity assays using cell culture and fluorometric methods. Results and conclusions. After dehydration and milling of the fruit endocarp, water was added to the obtained powder (in the ratio 4:1) to extract the dye. Five compounds were elucidated using HPLC-MS/MS and confirmed the presence of the geniposide as its main compound. With the X-ray diffraction and electron microscopy analysis, we characterised the obtained powder as being amorphous and of porous structure with a variable size. The thermogravimetric analysis indicated a maximum loss of 61% mass after exposure to a temperature range from 240 to 760 °C. The obtained blue dye was stable in the absence of light, at room temperature and had neutral pH. In the cytotoxicity assay, (95.0±1.3) % of viable human fibroblasts were observed after exposure to this dye. The genipap fruit can be a viable alternative to produce a natural blue dye, since it is easy to obtain and has very low toxicity in food, pharmaceutical or cosmetic products. Novelty and scientific contribution. This study demonstrates for the first time the physicochemical and biological properties of a natural blue dye from G. americana fruit.Pozadina istraživanja. Na tržištu se povećala potražnja za prirodnim bojilima. Njihova je prednost nad sintetičkima ta da potječu iz održivih izvora, pa su od velikog interesa za prehrambenu i kozmetičku industriju. Stoga je bitno razvijati nova prirodna bojila, te dodatno ispitati postojeća. Eksperimentalni pristup. Svrha je ovoga rada bila ispitati fizikalno-kemijska i biološka svojstva bojila dobivenog ektrakcijom dehidriranog endokarpa ploda biljke jagua (Genipa americana), te testirati njegovu stabilnosti i citotoksičnost. Kemijska svojstva određena su spregnutim sustavom visokodjelotvorne tekućinske kromatografije i tandemne spektrometrije masa (HPLC-MS/MS). Stabilnost je ispitana spektrofotometrijom, a citotoksičnost pomoću staničnih kultura i fluorometrijom. Rezultati i zaključci. Nakon dehidriranja i meljave endokarpa jague, za ekstrakciju bojila dobiveni je prah pomiješan s 20 % vode. Metodom HPLC-MS/MS detektirano je pet spojeva, te je potvrđena prisutnost genipozida kao glavnog sastojka. Rendgenskom difrakcijom i elektronskom mikroskopijom struktura dobivenog praha okarakterizirana je kao amorfna i porozna, s česticama različitih veličina. Termogravimetrijskom je analizom utvrđen gubitak od 61 % mase praha nakon izlaganja temperaturama između 240 i 760 °C. Dobiveno je bojilo bilo stabilno u mraku, pri sobnoj temperaturi i neutralnoj pH-vrijednosti. U testu citotoksičnosti utvrđena je stopa preživljavanja fibroblasta od (95,0±1,3) % nakon njihovog izlaganja bojilu. Stoga je zaključeno da plod voćke jagua može poslužiti kao izvor prirodnog bojila za primjenu u prehrambenoj, farmaceutskoj i kozmetičkoj industriji, jer se jednostavno dobiva i ima vrlo malu toksičnost. Novina i znanstveni doprinos. U ovom su radu po prvi put opisana fizikalno-kemijska i biološka svojstva prirodnog bojila dobivenog iz ploda voćke G. americana

The evaluation of in vitro antichagasic and anti-SARS-CoV-2 potential of inclusion complexes of β- and methyl-β-cyclodextrin with naphthoquinone

Funding Information: The authors thank the Coordination for the Improvement of Higher Education Personnel (CAPES) and the National Council for Scientific and Technological Development (CNPq) for their financial support. This study was supported by the CAPES — number 88887.505029/2020–00 . Cecilia Gomes Barbosa receives a scholarship funded by CAPES — number 88887.643352/2021–00 . Publisher Copyright: © 2023 Elsevier B.V.The compound 3a,10b-dihydro-1H-cyclopenta[b]naphtho[2,3-d]furan-5,10-dione (IVS320) is a naphthoquinone with antifungal and antichagasic potential, which however has low aqueous solubility. To increase bioavailability, inclusion complexes with β-cyclodextrin (βCD) and methyl-β-cyclodextrin (MβCD) were prepared by physical mixture (PM), kneading (KN) and rotary evaporation (RE), and their in vitro anti-SARS-CoV-2 and antichagasic potential was assessed. The formation of inclusion complexes led to a change in the physicochemical characteristics compared to IVS320 alone as well as a decrease in crystallinity degree that reached 74.44% for the IVS320-MβCD one prepared by RE. The IVS320 and IVS320-MβCD/RE system exhibited anti-SARS-CoV-2 activity, showing half maximal effective concentrations (EC50) of 0.47 and 1.22 μg/mL, respectively. Molecular docking simulation suggested IVS320 ability to interact with the SARS-CoV-2 viral protein. Finally, the highest antichagasic activity, expressed as percentage of Tripanosoma cruzi growth inhibition, was observed with IVS320-βCD/KN (70%) and IVS320-MβCD/PM (72%), while IVS320 alone exhibited only approximately 48% inhibition at the highest concentration (100 μg/mL).publishersversionpublishe

Cyclodextrin–Drug Inclusion Complexes: In Vivo and In Vitro Approaches

This review aims to provide a critical review of the biological performance of natural and synthetic substances complexed with cyclodextrins, highlighting: (i) inclusion complexes with cyclodextrins and their biological studies in vitro and in vivo; (ii) Evaluation and comparison of the bioactive efficacy of complexed and non-complexed substances; (iii) Chemical and biological performance tests of inclusion complexes, aimed at the development of new pharmaceutical products. Based on the evidence presented in the review, it is clear that cyclodextrins play a vital role in the development of inclusion complexes which promote improvements in the chemical and biological properties of the complexed active principles, as well as providing improved solubility and aqueous stability. Although the literature shows the importance of their ability to help produce innovative biotechnological substances, we still need more studies to develop and expand their therapeutic properties. It is, therefore, very important to gather together evidence of the effectiveness of inclusion complexes with cyclodextrins in order to facilitate a better understanding of research on this topic and encourage further studies

Inclusion Complexes of β and HPβ-Cyclodextrin with α, β Amyrin and In Vitro Anti-Inflammatory Activity

α, β amyrin (ABAM) is a natural mixture of pentacyclic triterpenes that has a wide range of biological activities. ABAM is isolated from the species of the Burseraceae family, in which the species Protium is commonly found in the Amazon region of Brazil. The aim of this work was to develop inclusion complexes (ICs) of ABAM and β-cyclodextrin (βCD) and hydroxypropyl-β-cyclodextrin (HPβCD) by physical mixing (PM) and kneading (KN) methods. Interactions between ABAM and the CD’s as well as the formation of ICs were confirmed by physicochemical characterization in the solid state by Fourier transform infrared (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetry (TG) and differential scanning calorimetry (DSC). Physicochemical characterization indicated the formation of ICs with both βCD and HPβCD. Such ICs were able to induce changes in the physicochemical properties of ABAM. In addition, the formation of ICs with cyclodextrins showed to be an effective and promising alternative to enhance the anti-inflammatory activity and safety of ABAM

Controle estatístico de processo univariado: monitoramento da produção de comprimidos de dipirona

Investigou-se, através de histogramas e cartas de controle X e S, a ferramenta do Controle Estatístico de Processo (CEP) univariado e os parâmetros físicos dureza, peso médio e friabilidade da produção de dez lotes de dipirona sódica comprimidos. Por sua complexidade e influência no processo, a etapa de granulação de cada lote foi concomitantemente caracterizada através de determinações de densidade bruta, densidade compactada, índice de compressibilidade e fator de Hausner, além dos ângulos de repouso, tempos de escoamento e repartições granulométricas. As caracterizações dos granulados serviram como base na investigação da possível influência da etapa de granulação como uma das prováveis causas que poderiam levar o processo a se apresentar fora de controle estatístico. Os resultados da caracterização indicaram certa uniformidade entre os granulados, o que pode significar que não há ligação aparente entre a etapa de granulação e a falta de controle estatístico do processo, demonstrada na avaliação das cartas de controle. Na medida em que permitiu uma maior compreensão do processo, o CEP univariado mostrou sua importância no monitoramento da produção de comprimidos. Palavras-chave: Controle Estatístico de Processo univariado. Monitoramento da produção. Indústria farmacêutica. Validação. ABSTRACT Univariate Statistical Process Control: monitoring the production of dipyrone tablets In this study, by means of histograms and and s control charts, the production control tool, univariate Statistical Process Control (SPC), was assessed for monitoring the physical variables hardness, weight and friability during the production of ten batches of sodium dipyrone tablets. In view of its complexity and influence on the process, the granulation step was concurrently characterized by determining the gross density, compacted density, compressibility index and Hausner factor, plus the angle of repose, flow time and particle size distributions of each batch. The properties of the granules were used as a basis for testing the hypothesis that the granulation step is probably the cause when the process runs out of statistical control. The results of the characterization indicated a degree of uniformity among the granules, which may mean that the lack of statistical process control demonstrated in the control charts does not arise from the granulation step. To the extent that it enabled a greater understanding of the process, univariate SCP proved its importance in the monitoring of tablet production. Keywords: Univariate Statistical Process Control. Production monitoring. Pharmaceutical industry. Validation

Development, Physicochemical Characterization and In Vitro Anti-Inflammatory Activity of Solid Dispersions of α,β Amyrin Isolated from Protium Oilresin

α,β Amyrin (ABAM) is a natural mixture of pentacyclic triterpenes that has shown a variety of pharmacological properties, including anti-inflammatory effect. ABAM is isolated from Burseraceae oilresins, especially from the Protium species, which is commonly found in the Brazilian Amazon. This work aimed to develop solid dispersions (SD) of ABAM with the following hydrophilic polymers: polyvinylpyrrolidone (PVP-K30), polyethylene glycol (PEG-6000) and hydroxypropylmethylcellulose (HPMC). The SDs were prepared by physical mixture (PM), kneading (KND) and rotary evaporation (RE) methods. In order to verify any interaction between ABAM and the hydrophilic polymers, physicochemical characterization was performed by Fourier transform infrared (FTIR), scanning electron microscopy (SEM), powder X-ray diffraction (XRD), thermogravimetry (TG) and differential scanning calorimetry (DSC) analysis. Furthermore, an in vitro anti-inflammatory assay was performed with ABAM alone and as SDs with the hydrophilic polymers. The results from the characterization analysis show that the SDs were able to induce changes in the physicochemical properties of ABAM, which suggests interaction with the polymer matrix. In vitro anti-inflammatory assay showed that the SDs improved the anti-inflammatory activity of ABAM and showed no cytotoxicity. In conclusion, this study showed the potential use of SDs as an efficient tool for improving the stability and anti-inflammatory activity of ABAM without cytotoxicity

In Silico Study, Physicochemical, and In Vitro Lipase Inhibitory Activity of α,β-Amyrenone Inclusion Complexes with Cyclodextrins

α,β-amyrenone (ABAME) is a triterpene derivative with many biological activities; however, its potential pharmacological use is hindered by its low solubility in water. In this context, the present work aimed to develop inclusion complexes (ICs) of ABAME with γ- and β-cyclodextrins (CD), which were systematically characterized through molecular modeling studies as well as FTIR, XRD, DSC, TGA, and SEM analyses. In vitro analyses of lipase activity were performed to evaluate possible anti-obesity properties. Molecular modeling studies indicated that the CD:ABAME ICs prepared at a 2:1 molar ratio would be more stable to the complexation process than those prepared at a 1:1 molar ratio. The physicochemical characterization showed strong evidence that corroborates with the in silico results, and the formation of ICs with CD was capable of inducing changes in ABAME physicochemical properties. ICs was shown to be a stronger inhibitor of lipase activity than Orlistat and to potentiate the inhibitory effects of ABAME on porcine pancreatic enzymes. In conclusion, a new pharmaceutical preparation with potentially improved physicochemical characteristics and inhibitory activity toward lipases was developed in this study, which could prove to be a promising ingredient for future formulations