Cocrystals Enhance Biopharmaceutical and Antimicrobial Properties of Norfloxacin.

A solvate cocrystal of the antimicrobial norfloxacin (NFX) was formed by using isonicotinamide (INA) as a coformer with the solvent evaporation technique. The cocrystal formation was confirmed by performing solid-state characterization techniques. We evaluated the dissolution under supersaturated conditions and also the solubility at the vertex of triphasic domain of cocrystal and NFX in both water and Fasted-State Simulated Intestinal Fluid (FaSSIF). The antimicrobial activity was evaluated using the microdilution technique. The cocrystal showed 1.8 times higher dissolution than NFX in water at 60 min and 1.3 times higher in FaSSIF at 180 min in the kinetic study. The cocrystal also had an increase in solubility of 8.38 times in water and 6.41 times in FaSSIF. The biopharmaceutical properties of NFX with cocrystallization improved antimicrobial action, as shown in the results of minimum inhibitory concentration (MIC) and inhibitory concentrations of 50% (IC50%) and 90% (IC90%). This paper presents, for the first time, a more in-depth analysis of the cocrystal of NFX-INA concerning its dissolution, solubility, and antimicrobial activity. In all these criteria, the cocrystal obtained better results compared to the pure drug.

Advanced formulations and nanotechnology-based approaches for pulmonary delivery of sildenafil: A scoping review.

Oral sildenafil (SDF) is used to treat pulmonary arterial hypertension (PAH), and its bioavailability is approximately 40%. Several formulations of nano and microparticles (for pulmonary delivery) are being developed because it is possible to improve characteristics such as release time, bioavailability, dose, frequency, and even directly target the drug to the lungs. This review summarizes the latest SDF drug delivery systems for PAH and explains challenges related to the development, the preclinical, and the clinical studies. A scoping review was conducted by searching electronic databases including PubMed, Scopus, and Web of Science to identify studies published between 2001 and 2021. From 300 articles found, 31 met the inclusion criteria. This review identified colloidal formulations such as polymeric, lipid, and metal-organic framework nanoparticles. Strategies were determined to reach the deep airways such as polymeric microparticles, large porous microparticles, nanocomposites, and nano in microparticles. Finally, aspects related to toxicological, pharmacokinetics, and gaps in information for potential use in humans were discussed. SDF formulations are significant candidates for the treatment of PAH by inhalation. In summation, future preclinical studies are still required in large animals, as there is no particular formulation yet submitted to clinical studies.

Comparator product issues for biowaiver implementation: the case of Fluconazole

The aim of this work was to assess if the commercially available Fluconazole drug products (Reference, Generic and Similar) would meet the biowaiver criteria from Food and Drug Administration (FDA) and Brazilian Agency for Health Surveillance (ANVISA) agencies. All formulations were evaluated considering the dissolution profile carried out in Simulated Gastric Fluid (SGF) pH 1.2, Acetate Buffer (AB) pH 4.5 and Simulated Intestinal Fluid (SIF) pH 6.8. The results demonstrated that all formulations fulfilled the 85% of drug dissolved at 30 min criterion in SGF pH 1.2. However, in AB pH 4.5 and SIF pH 6.8, some formulations, including the comparator, did not achieve this dissolution percentage. The discrepant dissolution profiles also failed the ƒ2 similarity factor analysis, since none of the formulations showed values between 50 and 100 in the three dissolution media. Comparative dissolution profiles were not similar, considering that the main issues concerning the dissolution were evidenced for the comparator product. Hence, a revision in the regulatory norms in order to establish criteria to switch the comparator could result in an increased application of drugs based on biowaiver criteria

Pharmaceutical applications of starch nanoparticles: A scoping review.

Starch nanoparticles (SNPs) have been applied to different areas of material sciences, especially in pharmaceuticals due to their characteristics such as small particle size, high surface ratio-volume, and biological compatibility. However, in pharmaceutical sciences, there are no records of a scoping review that had extensively mapped all available information about SNPs. A scoping review was performed here by searching electronic databases (Pubmed and Science Direct) to identify studies published previous to June 2020. From 699 total records, 37 matched the criteria for inclusion. The findings showed that SNPs have been used, not only for the development of different active pharmaceutical ingredient delivery systems, but also as an enzyme inhibitor, adsorption, and DNA precipitation agent. In conclusion, by combining different starch sources and methods SNPs show a remarkable diversity in pharmaceutical applications. Future studies should explore SNPs safety and provide information about variables that may affect important properties for this kind of application.

Myrcia hatschbachii: antifungal activity and structural elucidation of ellagic and 3-O-methyl ellagic acids.

Natural products, especially plants, have been investigated as sources of new substances with antimicrobial properties. In this context, the Myrcia genus is extensively researched for presenting such activities. This work aims to evaluate the antifungal, antibacterial, and antioxidant properties of extracts and fractions of stems of Myrcia hatschbachii, also to characterize two phenolic compounds. The antibacterial and antifungal activities were assessed by using the broth microdilution method. The ethyl acetate fraction (FGA) inhibited the growth of Candida albicans at a Minimum Inhibitory Concentration (MIC) of 15.6 µg/mL, presented 40% of phenolic compounds in its composition, obtained the most significant results in antioxidant methods (DPPH, FRAP, ABTS), besides the identification of ellagic and 3-O-methyl ellagic acids by NMR. Considering the relevant antifungal activity revealed by the fraction, new studies can be carried out to encourage the continuous search for antifungal alternatives.

Stability of bifidobacteria entrapped in goat's whey freeze concentrate and inulin as wall materials and powder properties.

Goat's whey was submitted to two cycles of block freeze concentration process, resulting in concentrate 1 and concentrate 2. Concentrate 1 was added with 5 g of inulin and both concentrates were inoculated with Bifidobacterium animalis ssp. lactis BB-12, the concentrates were then denoted as feed solutions 1 and 2, respectively. Feed solutions were spray-dried, resulting in powder 1 and 2. The stability of the bifidobacteria entrapped within the powders was evaluated for both spray-dried powders stored at 4 °C and 25 °C for 60 days. The spray-dried powders were also evaluated in relation to their physical and thermal properties. It was noted that Bifidobacteria displayed increased stability at refrigeration temperature. Analysis of physical properties indicated that the addition of inulin resulted in increased water solubility. However, both spray-dried powders displayed less flowability, as well as a yellow-greenish color. By evaluating the spray-dried powders thermal properties, it was possible to confirm that goat whey concentrates behave as excellent wall materials.

In Vitro Dissolution Profile of Dapagliflozin: Development, Method Validation, and Analysis of Commercial Tablets.

Dapagliflozin was the first of its class (inhibitors of sodium-glucose cotransporter) to be approved in Europe, USA, and Brazil. As the drug was recently approved, there is the need for research on analytical methods, including dissolution studies for the quality evaluation and assurance of tablets. The dissolution methodology was developed with apparatus II (paddle) in 900 mL of medium (simulated gastric fluid, pH 1.2), temperature set at 37 ± 0.5°C, and stirring speed of 50 rpm. For the quantification, a spectrophotometric (λ = 224 nm) method was developed and validated. In validation studies, the method proved to be specific and linear in the range from 0.5 to 15 µg·mL-1 (r2 = 0.998). The precision showed results with RSD values lower than 2%. The recovery of 80.72, 98.47, and 119.41% proved the accuracy of the method. Through a systematic approach by applying Factorial 23, the robustness of the method was confirmed (p > 0.05). The studies of commercial tablets containing 5 or 10 mg demonstrated that they could be considered similar through f1, f2, and dissolution efficiency analyses. Also, the developed method can be used for the quality evaluation of dapagliflozin tablets and can be considered as a scientific basis for future official pharmacopoeial methods.

In vitro photodynamic inactivation of conidia of the phytopathogenic fungus Colletotrichum graminicola with cationic porphyrins.

Photodynamic inactivation (PDI) is an efficient approach for the elimination of a series of microorganisms; however, PDI involving phytopathogenic filamentous fungi is scarce in the literature. In the present study, we have demonstrated the photoinactivating properties of five cationic meso-(1-methyl-4-pyridinio)porphyrins on conidia of the phytopathogen Colletotrichum graminicola. For this purpose, photophysical properties (photostability and (1)O2 singlet production) of the porphyrins under study were first evaluated. PDI assays were then performed with a fluence of 30, 60, 90 and 120 J cm(-2) and varying the porphyrin concentration from 1 to 25 µmol L(-1). Considering the lowest concentration that enabled the best photoinactivation, with the respective lowest effective irradiation time, the meso-(1-methyl-4-pyridinio)porphyrins herein studied could be ranked as follows: triple-charged 4 (1 µmol L(-1) with a fluence of 30 J cm(-2)) > double-charged-trans2 (1 µmol L(-1) with 60 J cm(-2)) > tetra-charged 5 (15 µmol L(-1) with 90 J cm(-2)) > mono-charged 1 (25 µmol L(-1) with 120 J cm(-2)). Double-charged-cis-porphyrin 3 inactivated C. graminicola conidia in the absence of light. Evaluation of the porphyrin binding to the conidia and fluorescence microscopic analysis were also performed, which were in agreement with the PDI results. In conclusion, the cationic porphyrins herein studied were considered efficient photosensitizers to inactivate C. graminicola conidia. The amount and position of positive charges are related to the compounds' amphiphilicity and therefore to their photodynamic activity.

Avaliação da qualidade microbiológica de maquiagens de uso coletivo / Microbiological quality evaluation of public use makeup

O mercado de cosméticos destaca-se no Brasil por apresentar crescimento mesmo diante da crise econômica. Devido ao constante aumento na utilização desses produtos é necessário avaliar a segurança microbiológica, especialmente para produtos de uso coletivo e, portanto, com maior risco de contaminação. O objetivo do presente trabalho foi avaliar a qualidade microbiológica de amostras de cosméticos para maquiagem, de uso coletivo, da cidade de Curitiba, Paraná. Foram analisadas quinze (15) amostras coletadas durante o período de janeiro a agosto de 2015. As análises microbiológicas foram realizadas segundo o Guia ABC de Microbiologia, objetivando a contagem de microrganismos viáveis totais e a pesquisa de patógenos. Quanto à contagem de microrganismos todas as amostras encontram-se dentro dos limites especificados pela legislação vigente. No entanto, três amostras apresentaram contaminação por microrganismo patogênico Staphylococcus coagulase positiva. Em indivíduos adultos saudáveis a utilização de cosméticos contaminados pode não representar sérios riscos, a menos que o organismo seja um patogênico primário, não sendo o caso do gênero Staphylococcus. Entretanto, pode representar perigo para pessoas com sistema imunológico fragilizado. Sendo assim, os conservantes utilizados para as preparações cosméticas permanecem eficazes mesmo após o seu uso coletivo, não apresentando sérios riscos a indivíduos adultos saudáveis.

The Brazilian cosmetics industry continues to grow despite the country's economic crisis. Due to the increasing use of these products, there is the need to evaluate their microbiological safety, especially for cosmetics of shared use regarding the risk of contamination. The aim of this study was to evaluate the microbiological quality of shared makeup samples in the city of Curitiba - Parana, Brazil. Fifteen samples were collected from January to August 2015. The microbiological investigation was performed according to ABC Microbiology Guide aiming at the total viable microorganism and pathogen count. Regarding the microorganism count, all samples were within the limits specified by law. However, tree samples were contaminated by positive coagulase Staphylococcus. This can pose danger to people with weakened immune systems. Thus, it can be concluded that the preservatives used in the preparation of cosmetics remain effective even after their shared use, and therefore, they do not present serious risk to healthy adults.

Avaliação da atividade antioxidante e antimicrobiana do extrato etanólico bruto e frações orgânicas obtidas a partir da casca do caule da espécie Guettarda uruguensis Cham, & Scthdl, (Rubiaceae) / Assessment of the antioxidant and antimicrobial activity of the crude ethanolic extract and organic fractions obtained from the stem bark of the specie Guettarda uruguensis Cham. & Scthdl. (Rubiaceae)

Este trabalho teve como objetivo avaliar o potencial antioxidante e antimicrobiano do extrato bruto e frações obtidas das cascas do caule da espécie Guettarda uruguensis, Os ensaios antioxidantes indicaram alto potencial antioxidante, No ensaio de redução de fosfomolibdênio, a fração acetato de etila apresentou atividade antioxidante de 41,67% em relação ao padrão de ácido ascórbico e superou em 35,21% a atividade do padrão rutina, No ensaio de redução do DPPH (2,2-diphenyl-1-picrylhydrazyl), a fração acetato de etila apresentou um IC50 de 10,91 µg mL-1, valor próximo ao do ácido ascórbico (IC50 = 4,78 µg mL-1) e da rutina (IC50 = 6,62 µg mL-1), Pelo ensaio de TBA (acido tiobabitúrico) o extrato bruto (IA = 71,48%) e a fração hexano (IA = 47,85%) apresentaram índices superiores ao controle de BHT (butil hidroxi tolueno) (IA = 42,66), Através do ensaio de microdiluição em placas, foi observado que o extrato bruto e frações apresentaram atividade antimicrobiana, O estudo fitoquímico qualitativo revelou a presença de alcaloides, cumarinas, esteroides e/ou triterpenos, heterosídeos saponínicos, taninos e aminogrupos...

This main purpose of this study was to evaluate the antimicrobial and antioxidant effects of the crude extract and fractions obtained from the stem bark of the plant species. The antioxidant assays indicated high antioxidant capacity. In the reduction assay of the phosphomolybdenum, the ethyl acetate fraction showed antioxidant activity of 41.67% compared to standard ascorbic acid and exceeded in 35.21% the activity of the standard rutin. In the reduction assay of the DPPH (2,2-diphenyl-1-picrylhydrazyl), the ethyl acetate fraction showed an IC50 of 10.91 µg mL-1, equivalent to the ascorbic acid (IC50 = 4.78 µg mL-1) and rutin (IC50 = 6.62 µg mL-1). By the TBA (thiobarbituric acid) assay the crude extract (IA = 71.48%) and hexane fraction (IA = 47.85%) had an index higher than the control of BHT (butyl hydroxy toluene) (IA = 42.675). Through of assay of microdilution on plates was verified that the crude extract and fractions showed antimicrobial activity. The qualitative phytochemical study revealed the presence of alkaloids, coumarins, steroids and/or triterpenoids, saponin glycosides, tannins and amino groups...

Development of a multiparticulate system containing enteric-release mini-tablets of omeprazole

The main aim of this study was to develop a multiparticulate system containing mini-tablets of omeprazole formulated with an enteric polymer with pH-dependent solubility. Pre-formulation studies showed good flow and compaction capacity, leading to the production ofhigh quality mini-tablets. The mini-tablets were coated in a fluidized bed with hydroxypropylmethylcellulose /Eudragit(r) L30D55 and packed into hard gelatin capsules. The dissolution profile showed gastro-resistance and zero-order kinetics. The dissolution profile for the formulation containing lactose as the diluent and coated with 12% (tablet weight gain) of polymer was similar to that ofthe reference drug.

O presente trabalho teve como objetivo desenvolver e avaliar um sistema multiparticulado de liberação modificada, composto por mini-comprimidos revestidos com polímero de liberação pH-dependente, utilizando como fármaco modelo o omeprazol. Os mini-comprimidos (diâmetro de 2,5 mm) foram obtidos em máquina de compresssão excêntrica, revestidos em leito fluidizado com hidroxipropilmetilcelulose/Eudragit(r)L30D55 e, em seguida, acondicionados em cápsulas gelatinosas duras. A partir dos resultados obtidos no perfil de dissolução foi possível demonstrar a liberação gastro-resistente e comportamento cinético de ordem zero. A formulação contendo lactose como diluente, com revestimento de 12% de polímero, demonstrou semelhança com o medicamento referência.

In vitro release of diclofenac diethylamine from gels: evaluation of generic semisolid drug products in Brazil

In order for the pharmacological action of a topical dermal drug product to occur, the drug must first be released from the vehicle to be available to penetrate the skin layers and reach the site of action. Drug release is mainly dependent on the characteristics of the formulation. Currently, to register a generic or a similar drug product in Brazil performance testing of topical drug products for local action is not required. In this context, this aim of this study was to evaluate the in vitro release of commercial diclofenac diethylamine gel products available on the Brazilian pharmaceutical market, using the vertical diffusion cell method. Factors which may influence the test, such as the type of membrane used, and the effect of the formulation characteristics on the diffusion rate were evaluated. Brazilian legislation currently allows generic drug products to contain excipients other than the reference drug, which may affect the drug release from the vehicle. Only one of the four generic drug products tested could be considered equivalent to the reference Cataflam Emulgel®. The cellulose acetate and polyethersulfone membranes tested were found to be interchangeable in the in vitro release studies carried out on this product.

Para exercer ação farmacológica, medicamentos tópicos de aplicação cutânea precisam, primeiramente, liberar o fármaco do veículo, para que desta forma ele se torne disponível para penetração nas camadas da pele, até atingir seu local de ação. A liberação do fármaco do veículo depende principalmente das características da formulação. Até a presente data, para registrar um medicamento genérico ou similar no Brasil não se exigem testes de desempenho para produtos tópicos de ação local. O presente trabalho teve como objetivo avaliar a liberação in vitro de especialidades farmacêuticas de diclofenaco dietilamônio gel do mercado farmacêutico brasileiro, usando o sistema de célula de difusão vertical. Avaliaram-se fatores que influenciam o teste como o tipo de membrana usada nos ensaios de liberação e características da formulação que impactam a velocidade de difusão. A legislação vigente no País permite que medicamentos genéricos contenham excipientes diferentes do medicamento referência. Esta diferença afetou a liberação do fármaco do veículo. Dos quatro medicamentos genéricos testados apenas um seria considerado equivalente ao medicamento referência Cataflam Emulgel®. As membranas de acetato de celulose e polietersulfona testadas apresentaram-se intercambiáveis nos estudos de liberação desse produto.

Essential Oils from Different Plant Parts of Eucalyptus cinerea F. Muell. ex Benth. (Myrtaceae) as a Source of 1,8-Cineole and Their Bioactivities.

Eucalyptus cinerea, known as silver dollar tree, has few descriptions in traditional medicine. Chemical composition and antimicrobial properties of the essential oils of leaves, flowers and fruits, collected seasonally, were determined by GC/MS and disk diffusion/MIC, respectively. 1,8-Cineole was the main compound, particularly in fresh leaves-Spring (74.98%), dried leaves-Spring (85.32%), flowers-Winter (78.76%) and fruits-Winter (80.97%). Other compounds were found in the aerial parts in all seasons: α-pinene (2.41% to 10.13%), limonene (1.46% to 4.43%), α-terpineol (1.73% to 11.72%), and α-terpinyl acetate (3.04% to 20.44%). The essential oils showed antimicrobial activities against bacteria and yeasts, with the best results being found for the dried autumn and winter leaves oils (MIC < 0.39 mg/mL) against Streptococcus pyogenes. For the other tested microorganisms the following MIC results were found: Staphylococcus aureus-Dried leaves oil from summer (0.78 mg/mL), Pseudomonas aeruginosa-Flowers oil from autumn and fruits oil from winter (1.56 mg/mL) and Candida albicans-Flowers oil from autumn and fruits oils from winter and spring (0.78 mg/mL).