Due to the highly dynamic and competitive environment, organizations are led to rethink their processes and strategies. In the industrial field, Lean Manufacturing (LM) is widely recognized as a traditional approach to eliminate waste in the value stream and ensure the efficiency of production processes. On the other hand, Industry 4.0 has recently emerged, incurring disruptive changes in manufacturing processes based on a technology-driven approach. The integration of these two philosophies to achieve organizational goals is interesting in order to guarantee competitiveness, especially for manu-facturing companies. This paper proposed an integration of LM tools and technologies 4.0, considering the perspectives of the industrial field in the digital era. Based on a three-step methodology, which included technological and industrial mapping, it was identified 25 synergy points. From interactions of LM tools mainly with Big Data Analytics, The Cloud, Virtual Simulation and Augmented Reality, multi-level circular diagrams pointed out the main contributions of Just in Time 4.0 (JIT 4.0), Kaizen 4.0, Kanban 4.0, Poka-Yoke 4.0, Value Stream Mapping 4.0 (VSM 4.0) and Total Productive Maintenance 4.0 (TPM 4.0). Also, five attributes of Lean 4.0 were identified, highlighting the integration between pro-cesses, devices and stakeholders; waste minimization; and autonomous, pointing to gains for the organization from this holistic integration approach.

No abstract

In this work, poloxamer (PL)-based binary hydrogels, composed of PL 407 and PL 188, were studied with regard to the physicochemical aspects of sol-gel transition and pharmaceutical formulation issues such as dissolution-release profiles. In particular, we evaluated the cytotoxicity, genotoxicity, and in vivo pharmacological performance of PL 407 and PL 407–PL 188 hydrogels containing tramadol (TR) to analyze its potential treatment of acute pain. Drug–micelle interaction studies showed the formation of PL 407–PL 188 binary systems and the drug partitioning into the micelles. Characterization of the sol-gel transition phase showed an increase on enthalpy variation values that were induced by the presence of TR hydrochloride within the PL 407 or PL 407–PL 188 systems. Hydrogel dissolution occurred rapidly, with approximately 30%–45% of the gel dissolved, reaching ~80%–90% up to 24 hours. For in vitro release assays, formulations followed the diffusion Higuchi model and lower K rel values were observed for PL 407 (20%, K rel =112.9±10.6 μg·h −1/2 ) and its binary systems PL 407–PL 188 (25%–5% and 25%–10%, K rel =80.8±6.1 and 103.4±8.3 μg·h −1/2 , respectively) in relation to TR solution (K rel =417.9±47.5 μg·h −1/2 , P <0.001). In addition, the reduced cytotoxicity (V79 fibroblasts and hepatocytes) and genotoxicity (V79 fibroblasts), as well as the prolonged analgesic effects (>72 hours) pointed to PL-based hydrogels as a potential treatment, by subcutaneous injection, for acute pain.

No abstract

No abstract

Budesonide (BUD) is a glucocorticoid widely used for the treatment of ulcerative colitis. In this work, we propose the study of the system BUD-HP-β-CD inclusion complex incorporated into PL 407 and PL407-PL403 thermoreversible hydrogels, considering physico-chemical and pharmaceutical aspects. Complexation between BUD and HP-β-CD was confirmed by phase solubility studies (1:1 stoichiometry, Kc=8662.8 M(-1)), DSC, FTIR and microscopy analyzes. BUD solubility in simulated upper and lower colon fluids was improved in a dependence of HP-β-CD and PL 407 or PL407-PL403 association. Micellar hydrodynamic diameter studies showed the interaction between HP-β-CD and PL blocks, as well as the reorganization of the micellar system in the presence of BUD and its inclusion complex. Micellization temperature (Tm) was not shifted, but sol-gel phase transition studies showed that in the presence of BUD, HP-β-CD or BUD:HP-β-CD complex, the association PL407-PL403 favored the gel formation close to the physiological temperature. Physico-chemical and in vitro release assays studies revealed no competitive displacement of BUD from the HP-β-CD cavity evoked by PL407 or PL407-PL403 addition. These findings point out the BUD-HP-β-CD in PL-based hydrogels as strategies for future investigations on development of new pharmaceutical formulations for the treatment of ulcerative colitis.

Resumo Historicamente, o cenário farmacêutico mundial tem sido dominado por grandes multinacionais (Big Pharma), majoritariamente de origem europeia e norte-americana. Contudo, é consenso na literatura a importância crescente dos mercados farmacêuticos emergentes (países farmaemergentes), especialmente China e Brasil, que são vistos como os maiores responsáveis pelo crescimento sustentável do segmento farmacêutico. Esse artigo teve como objetivo realizar um mapeamento tecnológico e industrial do setor farmacêutico, a partir de informações de bancos de dados patentários internacionais (WIPO e Derwent), entre 1996 até o último ano de registro (2013). Utilizando-se o Método dos Mínimos Quadrados e implementação de um algoritmo no MATLAB, desenvolveram-se previsões para o período 2014-2018. Os resultados obtidos atestaram a liderança da Europa e dos EUA no setor, destacando-se o índice de inovação da Hoffmann-La Roche; a participação expressiva da China; e a pouca contribuição do Brasil no âmbito mundial. Todavia, estimou-se uma tendência de crescimento acentuado no número de proteções concedidas ao Brasil (41%) e à China (27%), apontando um alcance, até 2036, dos índices de patenteamento chineses aos números dos atuais líderes mundiais, trazendo a esperança da difusão tecnológica e científica e do aumento da competitividade no segmento farmacêutico.

No abstract