Pharmaceutical evaluation of compounded furosemide capsules and excipient performance

Abstract Compounding pharmacies play an important role not only in compounding personalized formulations, but also preparing drugs at the same concentration and dosage as those from commercial manufacturers. The excipients used in compounding are generally standardized for many drugs, however they do not consider the intrinsic properties, such as the poor water solubility, of each substance. The excipient performance of commercially available compounded furosemide capsules in 7 compounding pharmacies from Manaus was evaluated and compared them to the performance of the reference medicinal product (Lasix® tablets) and 2 batches of capsules made in-house (T2 and T4) with a standardized excipient. All batches were subjected to tests for weight variation, assay, uniformity of dosage units, disintegration and dissolution profile. Of the 7 different compound formulas acquired in the compounding pharmacies, only 2 passed all tests. Most formulas passed the tests for weight determination, disintegration time and assay, however batches from 2 establishments failed in regards to the uniformity of the content and 5 batches failed the dissolution test. The reference medicinal product was approved in all tests, as were the T2 capsules made in-house with drug-excipient ratio 1:2. These results confirm the importance of the excipient composition, especially for poorly soluble drugs.

Anti-inflammatory effects and acute oral toxicity of Copaifera spp. essential oil-loaded nanoemulsion / Efectos antiinflamatorios y toxicidad oral aguda de nanoemulsión cargada de aceite esencial de Copaifera spp

Copaifera spp. essential oil (EOC) was extracted by hydrodistillation of Copaifera oleoresin (COR). The EOC was characterized by GC/MS and a novel EOC-loaded nanoemulsion was developed to enhance the EOC solubility and to evaluate its utility as antinflammatory. EOC contain 14 volatile compounds (including ß-caryophyllene: 51.52%) having a required HLB of 11. The Surfactant: EOC: Water ratio of 13:15:75 (%, w:w:w) produced the optimal formulation (particle size: 94.47 nm). The EOC-loaded nanoemulsion presented a pseudoplastic/thixotropic behavior with excellent shelf stability for 6 months. The anti-inflammatory effect of the nanoemulsion was more potent than that of the EOC, and statistically equal to diclofenac (50 mg/kg). The EOC-loaded nanoemulsion showed no oral acute toxicity (in mice) at 2000 mg/kg; hence, it is considered a nontoxic product. The development of the EOC-loaded nanoemulsion added value to both the COR and the EOC by providinga suitable formulation that could be used as an anti-inflammatory product.

El aceite esencial (EOC) fue extraído por hidrodestilación de oleoresina de Copaifera spp. El EOC fue caracterizado químicamente por GC/MS. Se formuló una nanoemulsión con EOC para mejorar la solubilidad del EOC y evaluar su utilidad como antiinflamatorio. El EOC contiene 14 compuestos volátiles (incluido el ß-cariofileno: 51,52%) con un HLB requerido de 11. La relación Tensioactivo: EOC: Agua de 13:15:75 (%, p:p:p) produjo la formulación óptima (tamaño de partícula: 94,47 nm).. La nanoemulsión cargada con EOC presentó un comportamiento pseudoplástico/tixotrópico con una excelente estabilidad en almacenamiento durante 6 meses. El efecto antiinflamatorio de la nanoemulsión fue más potente que el del EOC y estadísticamente igual al diclofenaco (50 mg/kg). La nanoemulsión cargada con COE no mostró toxicidad aguda oral (en ratones) a 2000 mg/kg; por lo tanto, se considera un producto no tóxico. El desarrollo de la nanoemulsión cargada con EOC agregó valor tanto al COR como al EOC al proporcionar una formulación adecuada que podría usarse como un producto antiinflamatorio.

Maytenus ilicifolia dry extract protects normal cells, induces apoptosis and regulates Bcl-2 in human cancer cells.

Maytenus is the largest genus of the family Celastraceae and the species Maytenus ilicifolia (popularly known as 'Espinheira Santa'). It is widely used in traditional Brazilian medicine to treat stomach conditions including nausea, gastritis, and ulcers. In this study, the apoptotic effects of a spray-dried extract of M. ilicifolia (SDEMI) was evaluated using human hepatocellular cells (HepG2), colorectal carcinoma cells (HT-29), and normal keratinocytes (HaCaT). Cells were treated with SDEMI for 4 and 24 h, then were assayed for levels of apoptosis, caspase-3, and Bcl-2 by flow cytometry, immunostaining, and Western blot, respectively. Significant differences between groups were determined using analysis of variance (P < 0.05). For HepG2 and HT-29 cells treated with SDEMI, various cytotoxic effects were observed compared with control cells at all timepoints assayed (P < 0.001). Furthermore, positive caspase-3 staining and down-regulation of Bcl-2 were observed, consistent with the induction of cell death detected in these cell lines. In contrast, treatment of HaCaT cells with SDEMI was associated with a protective effect compared with control cells at both timepoints (P < 0.001). For example, increased expression of Bcl-2 and negative caspase-3 staining were detected. Taken together, these results suggest that SDEMI protects normal cells, while SDEMI mediates induction of apoptosis via down-regulation of Bcl-2 and involvement of caspase-3 in human carcinoma cells.

Herbal mouthwash based on Libidibia ferrea: microbiological control, sensory characteristics, sedimentation, pH and density / Enxaguatório bucal fitoterápico à base de Libidibia ferrea: controle microbiológico, características organolépticas, sedimentação, pH e densidade

Introduction: Phytotherapy is the study of herbal medicines and their applicability to cure diseases in general, being a therapeutic method which can be used for the prevention and treatment of mouth diseases. Among the herbal studied, the Libidibia ferrea, known as jucá or ironwood, is widely used in folk medicine by presenting anti-inflammatory, analgesic, antimicrobial and antipyretic therapeutic properties. Objective: To evaluate in vitro pharmacological stability of the Libidibia ferrea extract's mouthwash (INPA - 228 022). Material and method: It was held the mouthwash microbiological control by determining the total number of microorganisms and Salmonella sp, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus; stability characteristics (color, odor, brightness and consistency), sedimentation test (centrifuge), the pH measurement (pH meter) and density evaluation (pycnometer) were analyzed. Result: The mouthwash showed to be absent from microorganisms and no changes were observed in the organoleptics and sedimentation characteristics. The average pH values were 6.21, 6.15 and 5.85 at 0, 30 and 60 days, respectively, and 1.029, 1.033 and 1.035 g/ mL density values, respectively, without interfering with the final characteristic of the formulation. Conclusion: The mouthwash presented pharmacological stability and quality conditions. .

Introdução: A Fitoterapia é o estudo de plantas medicinais e suas aplicabilidades para a cura de doenças em geral, constituindo um método terapêutico que pode ser utilizado para a prevenção e tratamento de doenças bucais. Dentre as plantas estudadas, a Libidibia ferrea, conhecida como jucá ou pau ferro, é bastante utilizada na medicina popular por apresentar propriedades terapêuticas anti-inflamatória, analgésica, antimicrobiana e antitérmica. Objetivo: Avaliar, in vitro, a estabilidade farmacológica de um enxaguatório bucal fitoterápico à base do extrato de Libidibia ferrea (228.022 - INPA). Material e método: Foi realizado o controle microbiológico do enxaguatório através da determinação do número total de microrganismos de Salmonella sp., Escherichia coli, Pseudomonas aeruginosa e Staphylococcus aureus; foram analisadas as características organolépticas (cor, odor, brilho e consistência), sedimentação (centrífuga), aferição do pH (peagâmetro) e densidade (picnômetro). Resultado: O enxaguatório mostrou-se ausente de microrganismos e não foram observadas alterações das características organolépticas e sedimentação. Os valores médios de pH foram de 6,21, 6,15 e 5,85 nos tempos de armazenamento de 0, 30 e 60 dias, respectivamente, e de densidade 1,029, 1,033 e 1,035 g/ mL, respectivamente, porém sem interferência na característica final da formulação. Conclusão: O enxaguatório à base de Libidibia ferrea apresentou condições de estabilidade e qualidade farmacológicas. .

Development of granules from phyllanthus niruri spray-dried extract / Desenvolvimento dos grânulos de extrato phyllanthus niruri seco por aspersão

The aim of this study was to develop granules from Phyllanthus niruri spray-dried extract using dry and wet granulation and to assess techniques to enable the production of granules with improved technological characteristics and yields. Granules were characterized by granulometry, reological parameters, compression and hygroscopic behavior. Independent of the granulation technique, technologically developed granules presented particle diameter, bulk and tapped densities and compressibility indexes suitable for a solid dosage form. The compression behavior showed plastic and fragmentary deformation for granules produced by the dry granulation technique and predominantly plastic deformation for wet granulation. Concerning the humidity sorption, the study showed that granules absorb less humidity than the spray-dried extract. However, granules with Eudragit® E 100 were the least hygroscopic.

O objetivo deste estudo foi desenvolver grânulos de extrato Phyllantus niruri seco por aspersão e por granulação úmida e avaliar técnicas que possibilitem a produção de grânulos com características tecnológicas e rendimentos aperfeiçoados. Os grânulos foram caracterizados por granulometria, parâmetros reológicos, compressão e comportamento higroscópico. Independentemente da técnica de granulação, os grânulos tecnologicamente desenvolvidos apresentaram diâmetro de partículas, densidades aparente e compactada e índices de compressibilidade adequados para a formulação sólida. O comportamento de compressão mostrou deformação plástica e elástica para os grânulos produzidos por técnicas de granulação seca e, predominantemente, deformação plástica para a granulação úmida. Com relação à absorção da umidade, o estudo mostrou que os grânulos absorvem menos umidade do que o extrato seco por aspersão. Entretanto, os grânulos com Eudragit E 100 foram os menos higroscópicos.

Development and optimization of extractives from Astronium urundeuva (allemão) Engl. by factorial design

The purpose of this study was to evaluate the influences from variables of preparation on dry residue and total tannins from macerates of Astronium urundeuva barks. Thus, a 3 ² factorial design was used to study the importance of plant proportion (10, 15 and 20 percent, w/v) and the ethanol concentration (40, 60 and 80 percent, v/v) on the selected response. Mathematical models were fitted according to experimental data. The validated equations were used to generate response surfaces. The analysis of the surfaces showed that the optimum conditions to obtain extractive preparations with high extractive efficiency for tannins were: 10 percent (w/v) of plant with ethanol 40 percent (v/v) as solvent.

O objetivo deste trabalho foi avaliar as influências de variáveis de preparação de macerados das cascas de Astronium urundeuva sobre resíduo seco e teor de taninos totais. Desta forma, um desenho fatorial do tipo 3² foi empregado para avaliar a importância da proporção de planta (10, 15 e 20 por cento; m/v) e da concentração de etanol (40, 60 e 80 por cento; v/v) sobre as respostas eleitas. Modelos matemáticos foram ajustados aos dados experimentais. As equações validadas foram usadas para gerar superfícies de respostas. A análise das superfícies demonstrou que as condições ótimas para obtenção de preparações extrativas com elevada eficiência extrativa de taninos foram: 10 por cento (m/v) para planta e etanol 40 por cento (v/v) como solvente.