Nanoemulsion: process selection and application in cosmetics--a review.

In recent decades, considerable and continuous growth in consumer demand in the cosmetics field has spurred the development of sophisticated formulations, aiming at high performance, attractive appearance, sensorial benefit and safety. Yet despite increasing demand from consumers, the formulator faces certain restrictions regarding the optimum equilibrium between the active compound concentration and the formulation base taking into account the nature of the skin structure, mainly concerning to the ideal penetration of the active compound, due to the natural skin barrier. Emulsion is a mixture of two immiscible phases, and the interest in nanoscale emulsion has been growing considerably in recent decades due to its specific attributes such as high stability, attractive appearance and drug delivery properties; therefore, performance is expected to improve using a lipid-based nanocarrier. Nanoemulsions are generated by different approaches: the so-called high-energy and low-energy methods. The global overview of these mechanisms and different alternatives for each method are presented in this paper, along with their benefits and drawbacks. As a cosmetics formulation is reflected in product delivery to consumers, nanoemulsion development with prospects for large-scale production is one of the key attributes in the method selection process. Thus, the aim of this review was to highlight the main high- and low-energy methods applicable in cosmetics and dermatological product development, their specificities, recent research on these methods in the cosmetics and consideration for the process selection optimization. The specific process with regard to inorganic nanoparticles, polymer nanoparticles and nanocapsule formulation is not considered in this paper.

An innovative challenge test for solid cosmetics using freeze-dried microorganisms and electrical methods.

Freeze-dried bacteria and fungi were used as inoculum in 28 days' PET. An electrical method was used in replacement of the conventional plate count method. The use of freeze-dried microorganisms in association with the electrical method can minimize the workload and the variability involved in PET for cosmetic powders.

Avaliação de indicadores biológicos na validação de processos de esterilização de isoladores por peróxidos de hidrogênio / Assessment of biological indicators in the validation of isolator decontamination with hydrogen peroxide

Os isoladores permitem a aplicação de descontaminação por gases, resultando em ambiente estéril. Esta característica, adicionada a possibilidade de não interferência humana no processo, torna o emprego dos isoladores consideravelmente vantajosa quando comparada com a performance dos processos em salas limpas convencionais. A descontaminação empregando peróxido de hidrogênio é vantajosa em relação a outros métodos disponíveis uma vez que é de fácil remoção após aplicação; sendo água e oxigênio seus produtos de degradação, apresenta boa compatibilidade com materiais usualmente empregados nas áreas produtivas; e seu custo é relativamente baixo. O propósito deste estudo foi demonstrar que o Geobacillus stearothermophilus (ATCC 12980) é o microrganismo mais resistente quando comparado com microrganismos isolados presentes em áreas produtivas, assim como avaliar o melhor material a servir de suporte durante a validação do processo de descontaminação das superfícies internas do isolador e externas de materiais presentes. Bacillus sp., Micrococcus luteus, Corynebacterium sp., Staphylococcus sp. e Penicilium sp. foram os microrganismos que apresentaram maior incidência na área produtiva. Aço inoxidável é o material mais adequado a ser usado como suporte para o emprego do peróxido de hidrogênio, por ser inerte e o principal componente dos isoladores e por não demonstrar incompatibilidade com o agente esterilizante. Os resultados obtidos nesta etapa do estudo demonstraram que o Geobacillus stearothermophilus é o microrganismo mais resistente para ser utilizado na avaliação da eficácia do peróxido de hidrogênio quando comparado com aqueles microrganismos encontrados na flora normal. Adicionalmente, o melhor suporte é o aço inoxidável, significando que os indicadores biológicos comercialmente disponíveis neste material são a melhor opção para este propósito.

Isolators allow decontamination gases to be employed to create a sterile processing environment. This feature, added to the potential removal of human interference in the process, makes the use of isolators rather advantageous, compared to performing aseptic processes in conventional clean rooms. Decontamination with vaporized hydrogen peroxide (VHP) offers several advantages over other available methods, as it decomposes to water and oxygen and is thus easy to remove after use, is highly compatible with materials usually employed in production areas and it is relatively cheap. The aims of this study were to prove that Geobacillus stearothermophilus (ATCC 12980) is more resistant than microorganisms isolated from the normal production area flora and to determine the best material to serve as a support during validation of the decontamination of the inner surfaces of isolators and outer surfaces of materials inside them. Bacillus sp., Micrococcus luteus, Corynebacterium, Staphylococcus sp. and Penicillium sp. were the microorganisms of highest incidence among those identified in the production area. Stainless steel is the best material to be used as a support for the VHP treatment of specimens, as it is inert and the main component of isolators and showed no incompatibility with this sterilizing agent. The results obtained in this phase of the experiment proved that Geobacillus stearothermophilus is the most resistant microorganism with which to challenge the effectiveness of hydrogen peroxide, when tested against species of the normal flora. Secondly, the best support material is stainless steel, showing that the commercial bioindicators available on the market with this support material are scientifically proved to be the best choice for this purpose.

The efficacy and stability of five sanitizing agents challenged with reference microorganisms and clean area isolates / Eficácia e estabilidade de cinco agentes sanitizantes avaliados frente a microrganismos de referência e isolados de áreas limpas

The antimicrobial activity of five sanitizing agents employed in clean areas designated for the pharmaceutical manufacturing of sterile products was tested against nine microorganisms, including four microorganisms from the clean area microbiota. The method consisted of challenging 5 mL of each sanitizing agent - 70% isopropyl alcohol, 0.4% LPH®, 1.16% hydrogen peroxide, 4% hydrogen peroxide, 1% Bioper® and 5% phenol - with 0.1mL each of concentrated suspensions (105 ? 106 CFU/mL) of Staphylococcus aureus, Candida albicans, Corynebacterium sp., Micrococcus luteus, Escherichia coli, Aspergillus niger, Bacillus subtilis, Staphylococcus sp. and Bacillus sp. for 10 minutes, followed by serial dilutions and plating. The results demonstrated that the five agents were effective against S. aureus, C. albicans, Corynebacterium sp., and M. luteus. The same was true of E. coli, except that isopropyl alcohol showed low levels of inactivation. With A. niger, isopropyl alcohol, 0.4% LPH® and hydrogen peroxide were more effective and 5% phenol and 1% Bioper® less effective. 1% Bioper® and 4% hydrogen peroxide showed greater inactivation of Staphylococcus sp., Bacillus sp. and B. subtilis than the other agents. Against S. aureus, C. albicans, Corynebacterium sp. and M. luteus, 5% phenol showed similar activity to other agents, while with A. niger, B. subtilis, Staphylococcus sp. and Bacillus sp., it was similar to or less active than the other agents. It was demonstrated that two microorganisms from the clean area microbiota, Staphylococcus sp. and Bacillus sp., were the most difficult to eradicate, requiring more frequent application of hydrogen peroxide and 1% Bioper® than the other strains.

O objetivo deste estudo é avaliar a atividade antimicrobiana de cinco agentes sanitizantes empregados em áreas limpas construídas para a fabricação de produtos farmacêuticos estéreis contra nove microrganismos, incluindo quatro microrganismos oriundos da área limpa. A metodologia constituiu em desafiar 5 mL de cada agente sanitizante, álcool isopropílico 70%, LPH® 0,400%, peróxido de hidrogênio 1,160% e 4%, Bioper® 1% e fenol 5% com 0,1 mL de suspensão concentrada (105 ? 106 UFC/mL) de Staphylococcus aureus, Candida albicans, Corynebacterium sp., Micrococcus luteus, Escherichia coli, Aspergillus niger, Bacillus subtilis, Staphylococcus sp. e Bacillus sp. individualmente por 10 minutos, seguido de diluições seriadas e plaqueamento. Os resultados demonstraram que os cinco agentes sanitizantes foram efetivos contra S. aureus, C. albicans, Corynebacterium sp., e M. luteus. Os mesmos resultados foram observados com E. coli, exceto para o álcool isopropílico, que demonstrou baixos níveis de inativação. Contra A. niger, álcool isopropílico, 0.4% LPH® e peróxido de hidrogênio foram mais efetivos e fenol e Bioper® menos efetivos. Bioper® e peróxido de hidrogênio 4% demonstraram altos níveis de inativação de Staphylococcus sp., Bacillus sp. e B. subtilis quando comparados com outros agentes. Fenol demonstrou atividade antimicrobiana similar aos outros agentes contra S. aureus, C. albicans, Corynebacterium sp. e M. luteus. Contra A. niger, B. subtilis, Staphylococcus sp. e Bacillus sp., a atividade antimicrobiana do fenol foi similar ou inferior a dos outros agentes. Foi demonstrado que os microrganismos isolados da área limpa, Staphylococcus sp. e Bacillus sp., foram os que apresentaram maior dificuldade para inativar, sendo necessária a aplicação de peróxido de hidrogênio e Bioper® , com maior frequência.

Análise da carga microbiana de implantes mamários de silicone / Microbial load analysis in silicone gel breast implants

Silicone breast implants consist of biomaterials widely used in breast reconstitution surgeries or in mammary augmentation for esthetic reasons. A preliminary stage of the implant production process is vulcanization, which consists of heating the implant to 165±5ºC for approximately 9 hours. The aim of this work was to evaluate the bioburden of silicone breast implants prior to the vulcanization process and the decline in bioburden due to this process, and to confirm the sterility of the gel contained in the membrane. Breast implant production stages were evaluated by microbial counting in different steps, according to the USP 32 methodology. To evaluation of decrease in microbial load, spores strips were introduced inside the implant, and after vulcanization cycles the strips were removed from the implant. The strips were transferred to tubes containing TSB, followed by incubation for 7 days at 30-35ºC. The results obtained showed that the level of microbial contamination of gel implants is relatively low, and that vulcanization allowed for the inactivation of up to 108 spores. This study led us to the conclusion that vulcanization leaded to sterility of the gel inside the product. Thus, the final sterilizing process contributed to an increase in the Sterility Assurance Level.1.

Os implantes mamários de silicone constituem-se em biomateriais que têm sido amplamente utilizados em cirurgias para reconstituição da mama ou para o aumento do tamanho da mama por motivos estéticos. Uma etapa preliminar do processo produtivo do implante é a vulcanização, que consiste no aquecimento do implante a 165±5ºC por aproximadamente 9 horas. O objetivo deste estudo foi avaliar a carga microbiana dos implantes mamários de silicone antes do processo de vulcanização, o decaimento da carga microbiana neste processo e confirmar a esterilidade do gel contidointernamente à membrana. Os estágios do processo produtivo dos implantes mamários foram avaliados pela contagem microbiana em diferentes etapas, de acordo com a metodologia da USP 32. Para avaliação do decaimento da carga microbiana, tiras de esporos foram introduzidas no interior do implante e após os ciclos de vulcanização foram retiradas do implante. As tiras foram transferidas para tubos contendo TSB, seguidos pela incubação por 7 dias a 30-35ºC. Os resultados obtidos mostraram que o nível de contaminação microbiana dos implantes gelatinosos é relativamente baixo e que a vulcanização possibilitou a inativação de até 108 esporos. Este estudo nos leva à conclusão que a vulcanização levou à esterilidade do gel interno ao produto. Desta forma, o processo esterilizante final contribuiu para um aumento no Nível de Garantia de Esterilidade.1.

Validação de método de doseamento e aplicação em estudo de equivalência farmacêutica de solução injetável de metronidazol / Validation of metronidazole assay methods and application to study of pharmaceutical equivalence of injectable solutions of this drug

O presente trabalho tem por objetivos validar métodos por espectrofotometria de absorção no ultravioleta e cromatografia líquida de alta eficiência para o doseamento de metronidazol em solução injetável e aplicá-los em estudo de equivalência farmacêutica entre medicamento de referência, genérico e similar. Os métodos propostos para doseamento de metronidazol em solução injetável por espectrofotometria de absorção no ultravioleta e por cromatografia líquida de alta eficiência foram validados, mostrando especificidade / seletividade, linearidade e faixa linear, limite de detecção /quantificação, exatidão e precisão adequados para o uso pretendido. Os medicamentos foram avaliados quanto aos testes de determinação de pH, volume médio, identificação por espectrofotometria de absorção no infravermelho, identificação por cromatografia líquida de alta eficiência, esterilidade, endotoxinas bacterianas e doseamento por espectrofotometria de absorção no ultravioleta e por cromatografia líquida de alta eficiência. Os três medicamentos atenderam as especificações para os testes avaliados e, portanto, podem ser considerados apresentando equivalência farmacêutica.

The aim of this study was to validate analytical methods, based on UV absorption spectrophotometry and high performance liquid chromatography (HPLC), to assay metronidazole supplied in injectable solutions, and to employ these methods in a study of the pharmaceutical equivalence of the original brand name medicine (?reference?), generic and similar (brand) medicines. The methods proposed for the metronidazole assay were validated, showing adequate specificity/selectivity, linearity, linear range, detection and quantitation limits, accuracy and precision for the intended purpose. The injectable solutions were then tested to determine pH, volume and identity (by IR spectrophotometry), to verify sterility, detect bacterial endotoxins and assay the drug by the proposed UV spectrophotometric and HPLC methods. All three medicines met the requirements in all tests performed and, therefore, can be considered pharmaceutically equivalent.

Validação de método de doseamento para aciclovir eaplicação em estudo de equivalência farmacêutica decreme contendo aciclovir / Validation of acyclovir assay method and its use toverify pharmaceutical equivalence of creamscontaining acyclovir

O presente trabalho teve por objetivos validar método para o doseamento de aciclovir em creme por espectrofotometria de absorção no ultravioleta e aplicá-lo em estudo de equivalência farmacêutica entre medicamento de referência, genérico e similar. O método proposto para doseamento de aciclovir em creme por espectrofotometria de absorção no ultravioleta foi validado, mostrando especificidade/ seletividade, linearidade e faixa linear, limite de detecção /quantificação, exatidão e precisão adequados para o uso pretendido. Os medicamentos foram avaliados quanto aos testes de peso médio, limite de guanina por cromatografia em camada delgada, identificação por espectrofotometria de absorção no ultravioleta, contagem microbiana de bactérias e fungos, pesquisa de microrganismos patógenos e doseamento por espectrofotometria de absorção no ultravioleta. Os três medicamentos atenderam as especificações para os testes avaliados e, portanto, podem ser considerados equivalentes farmacêuticos.

The aim of this study was to validate a UV absorption spectrophotometric method to assay acyclovir in cream and to use it to verify the pharmaceutical equivalence of the original brand-name, generic and similar (brand) medicines. The method proposed for acyclovir cream was validated, showing adequate specificity/selectivity, linearity and linear range, detection and quantitation limits, accuracy and precision. The medicines were tested for average weight, guanine contents within limits (by thin-layer chromatography), drug identity (by UV spectrophotometry), bacterial and fungal counts and presence of pathogens, and were assayed by UV spectrophotometry. All medicines met the requirements in all these tests and can, therefore, be considered equivalent.

Sterilization by pure oxygen plasma and by oxygen-hydrogen peroxide plasma: an efficacy study.

Plasma is an innovative sterilization method characterized by a low toxicity to operators and patients, and also by its operation at temperatures close to room temperatures. The use of different parameters for this method of sterilization and the corresponding results were analyzed in this study. A low-pressure inductive discharge was used to study the plasma sterilization processes. Oxygen and a mixture of oxygen and hydrogen peroxide were used as plasma source gases. The efficacy of the processes using different combinations of parameters such as plasma-generation method, type of gas, pressure, gas flow rate, temperature, power, and exposure time was evaluated. Two phases were developed for the processes, one using pure oxygen and the other a mixture of gases. Bacillus subtilis var. niger ATCC 9372 (Bacillus atrophaeus) spores inoculated on glass coverslips were used as biological indicators to evaluate the efficacy of the processes. All cycles were carried out in triplicate for different sublethal exposure times to calculate the D value by the enumeration method. The pour-plate technique was used to quantify the spores. D values of between 8 and 3 min were obtained. Best results were achieved at high power levels (350 and 400 W) using pure oxygen, showing that plasma sterilization is a promising alternative to other sterilization methods.

Comparative sterilization effectiveness of plasma in O2-H2O2 mixtures and ethylene oxide treatment.

We investigated the influence of variable parameters of plasma sterilization and compared its effectiveness with that of ethylene oxide using a reactive ion etching plasma reactor at 13.56 MHz. Gases tested were pure oxygen and oxygen-hydrogen peroxide mixtures in 190/10, 180/20, and 160/40 sccm ratios with constant gas flow at 200 sccm, pressure at 0.100 torr, radio-frequency power at 25 W, 50 W, 100 W, and 150 W, and temperature below 60 degrees C. Ethylene oxide sterilization was performed using 450 mg/L at 55 degrees C, 60% humidity, and -0.65 and 0.60 kgf/cm2 pressure. The biological indicator was Bacillus atrophaeus ATCC 9372, with exposure times of 3 to 120 min. Observed D values were 215.91, 55.55, 9.19, and 2.98 min for pure oxygen plasma at 25 W, 50 W, 100 W, and 150 W, respectively. Oxygen-hydrogen peroxide plasma produced D values of 6.41 min (190/10), 6.47 min (180/20), and 4.02 min (160/40) at 100 W and 1.47 min (190/10), 3.11 min (180/20), and 1.94 min (160/40) at 150 W. Ethylene oxide processes resulted in a D value of 2.86 min. Scanning electron microscopy analyses showed damage to the spore cortex.

Evaluation of preservative systems in opthalmic suspension of polymyxin B and dexamethasone by linear regression.

An ophthalmic suspension of polymyxin B and dexametasone with 13 different preservative systems was evaluated by a linear regression method for rapid screening, using D-values. The products were challenged against Pseudomonas aeruginosa, Burkholderia cepacia, Staphylococcus aureus, Candida albicans and Aspergillus niger. Since linear regression showed correlation coefficients higher than 0.84 the decimal reduction time (D-value) was then calculated. The comparison of D-values obtained for each microorganism and each product led to the selection of the formula 9 = 10, which was selected to be submitted to the efficacy of antimicrobial preservation according to the European Pharmacopoeia.