Abstract The present work reports the implementation of the Hazard Analysis Critical Control Point (HACCP) methodology to analyze the water purification system of a pharmaceutical site, in order to assure the system quality and prevent failures. As a matter of fact, the use of HACCP for development and implementation of Quality Risk Management (QRM) is not usual in pharmaceutical plants and it is applied here to improve the performance of the water purification system of a polymerization pilot plant used to manufacture pharmaceutical grade polymer microparticles. Critical Control Points (CCP) were determined with the aid of a decision tree and questions were made to characterize whether identified hazards constitute actual CCPs and should be monitored. When deviations were detected, corrective actions were performed and action plans were used for following-up and implementation of corrective actions. Finally, microbiological and physicochemical parameters were analyzed and the obtained results were regarded as appropriate. Therefore, it is shown that HACCP constitutes an effective tool for identification of hazards, establishment of corrective actions and monitoring of the critical control points that impact the process and the quality of the final pharmaceutical product most significantly.

Abstract Gelatin is employed in pharmaceutical applications because of its biodegradability, biocompatibility and low toxicity. However, it may be necessary to promote gelatin crosslinking in order to develop drug release systems and extend release times. SEC analyses are used here for the first time to monitor the evolution of molar mass distributions of gelatins during treatment with glycerol and glucose in dispersed media. Unambiguous experimental evidence of gelatin crosslinking in presence of sugars and glycerol has yet to be presented. SEC results indicate that average molar masses decrease during gelatin treatment, while FT-IR analyses indicate that gelatins are subject to structural modifications during processing, which can explain the decrease of gelatin solubility after treatment. The results presented here indicate the importance of using SEC techniques to monitor gelatin crosslinking, as they seemingly contradict previously published results that make use of indirect measures for this purpose.

ABSTRACT This study evaluates the biosurfactant activity and emulsification ability of pea proteins isolated (Pisum sativum L.). The results showed that aqueous solutions containing the pea proteins isolated (PPI) reduce the water surface tension to 47mN/m, approximately. The use of spray dryer does not change the surfactant activity of the PPI because surface tension and CMC will not change. The PPI is thermally stable and can be used in processes that require temperatures between 4°C and 80°C, as industrial processes such as baking, ice cream and other formulation. The protein isolate and pea assessed emulsions with toluene and n-heptane were stable. Emulsions castor and linseed oil were not stable under the conditions reported in this paper. Therefore, despite the pea protein isolate is a surfactant it cannot be used in any industrial process. Both the food industry and in the biotechnology industry should evaluate the conditions for application of protein isolates from pea.

Tamoxifen (TXF) is currently the only hormonal agent used for treatment of breast cancer. Although very effective, TXF presents low solubility in water, which affects its absorption and bioavailability. A common strategy to overcome this barrier is the formulation of a drug delivery system (DDS) in order to increase the drug stability and improve the treatment effectiveness. Reversible addition-fragmentation chain transfer (RAFT) polymerization is the most versatile method of controlled/living radical polymerization (CLRP), allowing for synthesis of well-defined polymers and being adapted to a wide range of polymerization systems. Miniemulsion polymerization is a dispersed system that is commonly used to prepare nanoparticles (NP) with 50 to 500 nm of diameter. The aim of this work was to evaluate the effect of the in situ incorporation of TXF during miniemulsion conventional and RAFT polymerizations, using methyl methacrylate (MMA) as monomer. Although the in situ addition of TXF promoted a slight reduction of the reaction rate, it did not affect the final particle size distribution of the latex or the molecular weight control exerted by the RAFT agent. The obtained results suggest that in situ incorporation of TXF during the synthesis of polymer NP via RAFT polymerization allows for production of a polymer DDS for different uses, such as the breast cancer treatment.

Dentre as diversas técnicas para obter polímeros de maneira controlada, a técnica de Transferência Reversível de Cadeia por Adição-Fragmentação (RAFT) é tida como uma das mais versáteis, uma vez que é compatível com uma grande quantidade de monômeros, solventes, condições reacionais e sistemas de polimerização. Utilizando essa metodologia, é possível sintetizar polímeros com diversas arquiteturas e com excelente controle do tamanho das cadeias. Neste trabalho, é apresentada uma revisão da técnica de polimerização RAFT em sistemas de miniemulsão. As principais características da técnica de polimerização RAFT e uma ampla revisão dos estudos em miniemulsão são apresentadas, abrangendo mais de 152 referências. Também é abordado nesta revisão o uso da polimerização RAFT em miniemulsão para obtenção de polímeros para aplicações biotecnológicas.

Among the many techniques used to prepare polymers in a controlled manner, reversible addition fragmentation chain transfer polymerization (RAFT) is one of the most versatile, since this technique is compatible with a large number of monomers, solvents, reaction conditions and polymerization systems. Using this methodology, it is possible to synthesize polymers with a variety of architectures and with a high level of control of the molecular weight distribution. In this work, a review of RAFT polymerizations in miniemulsion systems is presented. The main characteristics of the RAFT polymerization technique and a comprehensive review of studies in miniemulsion are presented, comprising more than 152 references. The use of RAFT miniemulsion polymerizaton to obtain polymers for biotechnological applications is also discussed in detail.

Copolímeros de propeno com 1-hexeno e 1,5-hexadieno, contendo diferentes teores de comonômeros, foram obtidos utilizando técnicas de polimerização em lama e em massa com catalisadores Ziegler-Natta heterogêneos de alta atividade. Foram avaliadas densidade, propriedades térmicas e mecânicas finais e estrutura do polímero. Os estudos mostraram que a densidade dos polímeros, temperaturas de transição (fusão e cristalização), módulo de rigidez, massa molar média e a cristalinidade diminuem com a incorporação do comonômero, uma vez que as cadeias laterais reduzem a organização da estrutura do copolímero. Os efeitos de densidade são mais apreciáveis no material que contém 1,5-hexadieno, enquanto que a redução na solubilidade em xileno (XS) e os efeitos térmicos são mais evidentes nas amostras com 1-hexeno. Os resultados de ressonância nuclear magnética demonstram que a incorporação do 1,5-hexadieno leva à formação de estruturas cíclicas na cadeia polimérica e que o aumento dos teores de dieno levam à reticulação das cadeias, resultando na produção de material insolúvel nos solventes orgânicos usuais.

1-hexene/propene and 1,5-hexadiene/propene copolymers with different comonomer contents were produced through slurry and bulk polymerizations with high activity heterogeneous Ziegler-Natta catalysts. The density, thermal and mechanical properties and molecular structure of the final resins were characterized and showed that the copolymer density, characteristic transition temperatures, modulus, average molecular weights and crystallinity decreased as the comonomer content increased. Density effects were more pronounced when 1,5-hexadiene was used as the comonomer, while variations of the xylene soluble contents and of the characteristic transition temperatures were more pronounced in the presence of 1-hexene. These results can be explained in terms of the smaller regularity of the chain structure when comonomer molecules are incorporated. Particularly, NMR analyses indicated that both double bonds were incorporated when 1,5-hexadiene was the comonomer, leading to formation of cyclic structures. When the diene content increased, reticulation caused the production of insoluble polymer resins.

Microwave irradiation offers a clean, inexpensive, and convenient method of heating, which is an alternative way of introducing energy into chemical systems. In particular, applications of microwave irradiation technology for petroleum processing have been developed in the last twenty years. The main objective of this paper is to review the use of microwave irradiation technology as an alternative technique applied during petroleum refining and primary processing of petroleum fluids, presenting and discussing successful applications of this technology as a tool for petroleum emulsion separation and catalytic reactions normally found at hydrorefining plants.

A distribuição de pesos moleculares de resinas poliolefínicas é freqüentemente analisada em termos da existência de bimodalidades e com auxílio de técnicas de desconvolução. As condições necessárias para a obtenção de uma resina poliolefínica bimodal são apresentadas em função das características cinéticas dos sítios ativos presentes no catalisador, sendo que um certo grau de bimodalidade sempre pode ser definido para essas resinas. Distribuições de peso molecular de Schulz-Flory dinâmicas são neste trabalho derivadas para a utilização em problemas de desconvolução, quando a dinâmica da concentração de monômero não pode ser desprezada. É demonstrado que a utilização de distribuições de Schulz-Flory padrão, nestas condições, leva à detecção de sítios ativos inexistentes no sistema catalítico.

The deconvolution of molecular weight distributions (MWD) may be useful to obtain information about the polymerization kinetics and properties of catalytic systems. However, deconvolution techniques are normally based on steady-state assumptions and very little has been reported about the use of non-stationary approaches for deconvolution of MWDs. In spite of that, polymerization reactions are often performed in batch or semi-batch modes. For this reason, dynamic solutions are proposed here for simple kinetic models and are then used for deconvolution of actual MWD data. Deconvolution results obtained with dynamic models are compared to deconvolution results obtained with the standard stationary Flory-Schulz distributions. For coordination polymerizations, results show that dynamic MWD models are able to describe experimental data with fewer catalytic sites, which indicates that the proper interpretation of the reaction dynamics may be of fundamental importance for kinetic characterization. On the other hand, reaction dynamics induced by modification of chain transfer agent concentrations seems to play a minor role on the shape of the MWD in free-radical polymerizations