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The current treatment for cutaneous tuberculosis consists of oral coadministration of isoniazid (INH) and rifampicin, which is often related to hepatotoxic events. Alternatively, INH could be administered on the skin aiming to avoid or minimize these side effects. The high cutaneous permeation of this drug motivated the obtainment of a cocrystal of INH and resveratrol (RES), a lipophilic compound, to provide a local effect. In this study, isoniazid–resveratrol cocrystal (INH-RES) was synthesized by reaction crystallization method, and its structure was determined from single-crystal X-ray diffraction data. Cocrystal, drug, and coformer aqueous solubility was determined in the initial pH range from 1.2 to 7.4. Mathematical models based on cocrystal constituent ionization constants (pK a), solution pH, and cocrystal solubility product (K sp) were used to generate solubility diagrams as a function of pH. At all pH values studied, INH-RES was less soluble than INH. Permeation studies were performed with drug and cocrystal applied to porcine skin in Franz diffusion chambers. Cocrystal reduced the amount of permeated drug by 86%. The association with a coformer that has higher log P decreased INH permeation, highlighting the importance of considering the drug permeation route during the coformer selection.

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This study evaluated the performance, immunology, and survival of the Pacific white shrimp Litopenaeus vannamei to experimental challenge to Vibrio alginolyticus based on the use of the probiotic Lactobacillus plantarum and the combined use of probiotic and butyrate. Four different diets resulted from the addition of additives: butyrate, probiotic, butyrate + probiotic, and control (no additives). The attractiveness of the diets was assessed by the percentage of positive choices and rejections, using a dual-choice Y-maze format aquarium. The shrimps were fed during four weeks and performance parameters, intestinal microbiota, and immunological parameters were all evaluated. Subsequently, the shrimps were challenged with V. alginolyticus and after 48 h, survival and immunological parameters were evaluated. The results showed increased attractiveness and intake, but only with diets supplemented with sodium butyrate. However, other diets were not rejected. No difference in performance or immunological parameters was observed among the different diets. Also, among the treatments, no difference in Vibrio spp., or total heterotrophic bacteria counts, was found in the intestinal tract. However, the lactic acid bacteria count was higher in the intestinal tract of shrimps fed diets supplemented with probiotic. After bacterial challenge, shrimp fed all diets had a greater survival when compared with the control group. Lactobacillus plantarum and sodium butyrate increase the resistance of shrimp to infection with V. alginolyticus, but do so without affecting performance, immunological parameters, or Vibrio spp., and total heterotrophic bacteria counts in the intestinal tract.

COCRYSTALS: A PROMISING STRATEGY IN PHARMACEUTICAL SCIENCES. Pharmaceutical cocrystals have emerged as a useful strategy to improve the aqueous solubility of poorly water soluble drugs by aiming to enhance their oral absorption and bioavailability. Aqueous cocrystal solubility can be orders of magnitude higher than that of the constituent drug and this solubility advantage can be fine-tuned based on environmental conditions such as pH and the presence of drug solubilizing agents. This review presents a brief overview of pharmaceutical cocrystals regarding cocrystal design, obtainment methods, with particular focus on cocrystal solubility, and the solubility modulation by solution phase chemistry.Keywords: cocrystals; drug; solubility; transition point; thermodynamic stability. INTRODUÇÃOO setor de fármaco-medicamentos representa uma área estratégica sob o ponto de vista tecnológico/produtivo nacional. Vários são os desafios da produção de medicamentos competitivos e de qualidade no Brasil, como a oferta de insumos, a pesquisa de novas moléculas ativas e a sua inserção no mercado. Neste sentido, a utilização de inovações incrementais surge como alternativa à problemática do setor, destacando-se a manipulação da forma cristalina dos fármacos, síntese de polimorfos, sais, complexos e, mais recentemente, os cocristais. 1 Cocristais são materiais cristalinos homogêneos, compostos por dois ou mais compostos em proporção estequiométrica definida e que são sólidos em condições ambientes (25 ºC/1 atm). 2,3 Ao longo das últimas décadas, os cocristais têm recebido atenção significativa por parte da indústria farmacêutica, e diversos cocristais farmacêuticos têm sido relatados. Cocristais farmacêuticos, por sua vez, são compostos por um ingrediente farmacêutico ativo (IFA) e uma molécula não tóxica ou outro IFA, chamado de coformador. Ligações de hidrogênio entre as moléculas neutras do fármaco e do coformador orientam a formação do cocristal. 2,4 A síntese de cocristais tem sido uma estratégia cada vez mais utilizada para melhorar a solubilidade, a taxa de dissolução in vitro, e consequentemente, a biodisponibilidade de fármacos pouco solúveis, sem a necessidade de mudar a estrutura molecular e/ou a interação farmacológica. [5][6][7] No entanto, a avaliação da solubilidade e estabilidade dos cocristais em solução ainda não está consolidada. Um levantamento realizado no período de 1999 a 2015 (Figura 1) revelou um crescente número de publicações envolvendo a síntese e a caracterização dos cocristais, mas um reduzido número de publicações envolvendo outros aspectos essenciais no desenvolvimento de formulações contendo cocristais, como estudos de solubilidade, química em solução, estabilidade e a influência de excipientes.Considerando que a baixa solubilidade aquosa é um dos principais problemas associados às entidades químicas farmacêuticas, os

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Although innovation capabilities are essential to increase companies' success and innovative performance, they are still underexplored regarding sustainability. This paper aims to analyze how Technology Development, Operations, Management, and Transaction innovation capabilities are interrelated with sustainable companies' social, environmental, and economic sustainability. We performed a multi‐case study comprising sustainable small enterprises from four industries: sustainable fashion, sustainable hosting, shared furniture, and renewable energy. From the results, we propose that each innovation capability has three dimensions: social, environmental, and economic. Each dimension has a set of components that can differ across capabilities. We then develop a conceptual scheme, a new theoretical lens that intertwines the literature on innovation capabilities and sustainability. We propose the concepts of Sustainable Technology Development Capability, Sustainable Operations Capability, Sustainable Management Capability, and Sustainable Transaction Capability. Our findings can assist sustainable businesses to improve, and traditional companies to build, sustainable innovation capabilities.

Purpose: to investigate the entrepreneurial intention profile of the employees of startups and small companies in the technology segment of the State of Rio Grande do Sul, when they working to an organization. Methodology: descriptive research, using a quantitative approach, using the survey method. The data collection instrument was the questionnaire, based on the model by Kristiansen & Indarti (2004). Findings: the results demonstrate that more than 60% of the respondents intend to undertake, especially when perceiving themselves as a desired professional in the job market. Theoretical contributions: the study contributes theoretically to studies of entrepreneurial intent in Brazil, mainly because it provides a view outside the sphere of higher education institutions, the setting for most of the studies already published. Originality: when conducting a survey of data on Startups and Small Companies in the Technology segment, in the State of Rio Grande de Sul, it was found a small number of employees involved in the operations of these businesses, but with a good percentage interested in undertaking. Contributions to management: the study contributes to the advance of management in the sectors of startups and the technology area of Rio Grande do Sul, by identifying that incentive work and skills development can generate new business partnerships within the startups themselves, generating growth and competitive potential.