Micronization of Pharmaceuticals and Food Ingredients using Supercritical Fluid Techniques

Micronization techniques based on supercritical fluids (SCFs) are promising for the production of particles with controlled size and distribution. The interest of the pharmaceutical field in the development of SCF techniques is increasing due to the need for clean processes, reduced consumption of energy, and to their several possible applications. The food field is still far from the application of SCF micronization techniques, but there is increasing interest mainly for the processing of products with high added value. The aim of this study is to use SCF micronization techniques for the production of particles of pharmaceuticals and food ingredients with controlled particle size and morphology, and to look at their production on semi-industrial scale. The results obtained are also used to understand the processes from the perspective of broader application within the pharmaceutical and food industries. Certain pharmaceuticals, a biopolymer and a food ingredient have been tested using supercritical antisolvent micronization (SAS) or supercritical assisted atomization (SAA) techniques. The reproducibility of the SAS technique has been studied using physically different apparatuses and on both laboratory and semi-industrial scale. Moreover, a comparison between semi-continuous and batch mode has been performed. The behaviour of the system during the SAS process has been observed using a windowed precipitation vessel. The micronized powders have been characterized by particle size and distribution, morphology and crystallinity. Several analyses have been performed to verify if the SCF process modified the structure of the compound or caused degradation or contamination of the product. The different powder morphologies obtained have been linked to the position of the process operating point with respect to the vapour-liquid equilibrium (VLE) of the systems studied, that is, mainly to the position of the mixture critical point (MCP) of the mixture. Spherical micro, submicro- and nanoparticles, expanded microparticles (balloons) and crystals were obtained by SAS. The obtained particles were amorphous or with different degrees of crystallinity and, in some cases, had different pseudo-polymorphic or polymorphic forms. A compound that could not be processed using SAS was micronized by SAA, and amorphous particles were obtained, stable in vials at room temperature. The SCF micronization techniques studied proved to be effective and versatile for the production of particles for several uses. Furthermore, the findings of this study and the acquired knowledge of the proposed processes can allow a more conscious application of SCF techniques to obtain products with the desired characteristics and enable the use of their principles for broader applications.

Toxicity assessment of refill liquids for electronic cigarettes.

We analyzed 42 models from 14 brands of refill liquids for e-cigarettes for the presence of micro-organisms, diethylene glycol, ethylene glycol, hydrocarbons, ethanol, aldehydes, tobacco-specific nitrosamines, and solvents. All the liquids under scrutiny complied with norms for the absence of yeast, mold, aerobic microbes, Staphylococcus aureus, and Pseudomonas aeruginosa. Diethylene glycol, ethylene glycol and ethanol were detected, but remained within limits authorized for food and pharmaceutical products. Terpenic compounds and aldehydes were found in the products, in particular formaldehyde and acrolein. No sample contained nitrosamines at levels above the limit of detection (1 μg/g). Residual solvents such as 1,3-butadiene, cyclohexane and acetone, to name a few, were found in some products. None of the products under scrutiny were totally exempt of potentially toxic compounds. However, for products other than nicotine, the oral acute toxicity of the e-liquids tested seems to be of minor concern. However, a minority of liquids, especially those with flavorings, showed particularly high ranges of chemicals, causing concerns about their potential toxicity in case of chronic oral exposure.

A need for determination of arsenic species at low levels in cereal-based food and infant cereals. Validation of a method by LC-ICPMS.

The present study arose from the need to determine inorganic arsenic (iAs) at low levels in cereal-based food. Validated methods with a low limit of detection (LOD) are required to analyse these kinds of food. An analytical method for the determination of iAs, methylarsonic acid (MA) and dimethylarsinic acid (DMA) in cereal-based food and infant cereals is reported. The method was optimised and validated to achieve low LODs. Ion chromatography-inductively coupled plasma mass spectrometry (LC-ICPMS) was used for arsenic speciation. The main quality parameters were established. To expand the applicability of the method, different cereal products were analysed: bread, biscuits, breakfast cereals, wheat flour, corn snacks, pasta and infant cereals. The total and inorganic arsenic content of 29 cereal-based food samples ranged between 3.7-35.6 and 3.1-26.0 microg As kg-1, respectively. The present method could be considered a valuable tool for assessing inorganic arsenic contents in cereal-based foods.

Hermetic sealing of food packaging trays

Suojakaasupakkaaminen on lisääntynyt voimakkaasti viime vuosina elintarvikkeiden pakkaamisessa sillä pakkaamalla elintarvike suojakaasuun voidaan sen hyllyikää pidentää ilman säilöntäaineita. Tällainen pakkaaminen vaatii kuitenkin täysin kaasutiiviin pakkauksen, jonka kaasunläpäisevyys on myös alhainen. Yleisimmin käytetyt pakkausmateriaalit suojakaasupakkaamisessa ovat monikerroksiset muovimateriaalit, joissa yhdistyy monen eri muovin parhaimmat ominaisuudet. Yleisimmin käytettyjä muovilaatuja näissä monikerrosrakenteissa ovat PE, PET, PA ja EVOH polymeerit. Myös muita perinteisiä polymeerejä käytetään jonkin verran näissä rakenteissa. Uudemmat muovilaadut, kuten biohajoavat muovit, eivät ole vielä yleistyneet kaupallisessa käytössä pääasiallisesti niiden korkean hinnan vuoksi. Muovisten pakkausten korvaamista esimerkiksi muovipäällystetyillä kartonkipakkauksilla on viime vuosien aikana tutkittu enenevissä määrin. Muovipakkausten korvaamista helpommin kierrätettävillä ja mahdollisesti biohajoavilla materiaaleilla edistävät EU:n direktiivit, jotka käsittelevät pakkausjätteen käsittelyä. Kartonkivuokien saumaamista kaasutiiviisti tutkittiin myös tässä työssä. Tavoitteena oli löytää pakkaus, joka soveltuisi kanasuikaleiden pakkaamiseen suojakaasuun. Kana on herkkä mikrobiologiselle hajoamiselle, minkä johdosta se tulee pakata suojakaasuun jossa happipitoisuuden tulee olla alle 1 % pakkauspäivästä viimeiseen käyttöpäivään saakka. Suorittamalla erilaisia tiiveystutkimuksia voitiin osoittaa, että kartonkivuoka on mahdollista saumata kaasutiiviisti luotettavalla tavalla. Tämä vaatii kuitenkin kartonkivuokien valmistuksen optimoimista päällystemuovikerroksen ja kartongin paksuuden mukaan sekä kannen saumaamista optimoiduilla saumausparametreilla. Tiivein vuoka saavutettiin muovifilmikannella, jonka saumaus perustui samaan muoviin kuin vuoan saumaus. Polyeteenillä saavutettiin tiivein ja kestävin saumaustulos.

The effects of milk as a food matrix for polyphenols on the excretion profile of cocoa (-)-Epicatechin metabolites in healthy humans subjects

The effect of different food matrices on the metabolism and excretion of polyphenols is uncertain. The objective of the study was to evaluate the possible effect of milk on the excretion of (2)-epicatechin metabolites from cocoa powder after its ingestion with and without milk. Twenty-one volunteers received the following three test meals each in a randomised cross-over design with a 1-week interval between meals: (1) 250 ml whole milk as a control; (2) 40 g cocoa powder dissolved in 250 ml whole milk (CC-M); (3) 40 g cocoa powder dissolved in 250 ml water (CC-W). Urine was collected before consumption and during the 0-6, 6-12 and 12-24 h periods after consumption. (2)-Epicatechin metabolite excretion was measured using liquid chromatography-MS. One (2)-epicatechin glucuronide and three (2)-epicatechin sulfates were detected in urine excreted after the intake of the two cocoa beverages (CC-M and CC-W). The results show that milk does not significantly affect the total amount of metabolites excreted in urine. However, differences in metabolite excretion profiles were observed; there were changes in the glucuronide and sulfate excretion rates, and the sulfation position between the period of excretion and the matrix. The matrix in which polyphenols are consumed can affect their metabolism and excretion, and this may affect their biological activity. Thus, more studies are needed to evaluate the effect of these different metabolite profiles on the body.

Postmortem angiography using femoral cannulation and postmortem microbiology.

Despite the undeniable advantages of postmortem angiography, numerous questions have arisen concerning the influence that the injected contrast media may exercise on biological fluids and tissues collected for toxicological and biochemical investigations. Moreover, cardiac blood for microbiological investigations cannot be obtained post-angiography. In this study, we examined whether the peripheral blood collected prior to postmortem angiography, using percutaneous access to femoral vessels after skin surface disinfection, could be suitable for microbiological investigations when postmortem angiography with femoral vessel cannulation is also performed. A total of 66 cases were included in the study and were divided into two subgroups (angiography and bacteriology group, 33 cases and control group, 33 cases). Autopsies, histology, toxicology, bacteriology, and biochemical investigations (procalcitonin, C-reactive protein, interleukin-6, and soluble triggering receptors expressed on myeloid cells type 1) were performed in all cases. No statistically significant differences between the two groups were noted, and identified category distribution (death unrelated to infection, true infection, false positive, and undetermined) was rather similar in both studied populations. These preliminary results suggest that postmortem angiography using a femoral approach does not constitute an impediment to the collection of peripheral blood for microbiology and vice versa. Moreover, the use of femoral blood for microbiology does not lead to an increased risk of doubtful results.

The potential of different fruit species as food for Harmonia axyridis (Pallas, 1773) (Coleoptera: Coccinellidae)

Harmonia axyridis was detected for the first time in Brazil in 2002. Since then, it has been recorded from the South to the Midwest of the country. Until now, almost all the registered cases were associated with the presence of aphids, its preferred source of food. Due to the occurrence of this species in areas of fruit growing in the South and Southeast of Brazil, the aim of this study was to analyze the preference and use of three different cultivars of fruit. The tests were set at 25ºC ± 1ºC, RH 70% ± 10%, and in a photophase of 12 h and with apples (Gala and Fuji), grapes (Niágara and Rubi), and pears (Williams and Asian). In the undamaged fruit experiment, the insects did not cause any noticeable damage. In the damaged and undamaged fruit experiment, a higher and statistically significant percentage of H. axyridis adults were found in the three damaged fruits. In the different cultivar experiment the Niágara grape, the Gala apple, and the Williams pear were significantly preferred by H. axyridis adults. These results may help in the management of this insect, preventing damage, which have been observed in other places where H. axyridis was introduced.

The gender-based stereotype about food is on the table. Food choice also depends on co-eater's gender

Previous research has shown that different foods are stereotypically associated with gender and that eating in a role-congruent way fulfills an impression management function. On the other hand, other studies revealed that adapting one's food consumption to that of the co-eaters is a means to gain social approval as well. In the present study, we bridge these two distinct lines of research by studying what happens when the two norms (conforming to the gender-based stereotype and imitating the co-eater) conflict, that is with opposite-sex co-eaters. Results indicated that the tendency to match the co-eaters' supposed consumption generally appeared over and above one's gender-congruent choice. In addition, as expected, gender differences also emerged: while men were always willing to adapt to the co-eaters, women's intention to eat the feminine food was independent from the co-eaters' gender.

Patterns of primary growth increments in otoliths of Sparus aurata larvae in relation to water temperature and food consumption

Sparus aurata larvae reared under controlled water-temperature conditions during the first 24 days after hatching displayed a linear relationship between age (t) and standard length (SL): SL = 2.68 + 0.19 t (r2 = 0.91l). Increments were laid down in the sagittae with daily periodicity starting on day of hatching. Standard length (SL) and sagittae radius (OR) were correlated: SL(mm) = 2.65 + 0.012 OR(mm). The series of measurements of daily growth increment widths (DWI), food density and water temperature were analyzed by means of time series analysis. The DWI series were strongly autocorrelated, the growth on any one day was dependent upon growth on the previous day. Time series of water temperatures showed, as expected, a random pattern of variation, while food consumed daily was a function of food consumed the two previous days. The DWI series and the food density were correlated positively at lags 1 and 2. The results provided evidence of the importance of food intake upon the sagittae growth when temperature is optimal (20ºC). Sagittae growth was correlated with growth on the previous day, so this should be taken into account when fish growth is derived from sagittae growth rates.

Gut physiology mediates a trade-off between adaptation to malnutrition and susceptibility to food-borne pathogens.

The animal gut plays a central role in tackling two common ecological challenges, nutrient shortage and food-borne parasites, the former by efficient digestion and nutrient absorption, the latter by acting as an immune organ and a barrier. It remains unknown whether these functions can be independently optimised by evolution, or whether they interfere with each other. We report that Drosophila melanogaster populations adapted during 160 generations of experimental evolution to chronic larval malnutrition became more susceptible to intestinal infection with the opportunistic bacterial pathogen Pseudomonas entomophila. However, they do not show suppressed immune response or higher bacterial loads. Rather, their increased susceptibility to P. entomophila is largely mediated by an elevated predisposition to loss of intestinal barrier integrity upon infection. These results may reflect a trade-off between the efficiency of nutrient extraction from poor food and the protective function of the gut, in particular its tolerance to pathogen-induced damage.

Phenol-Explorer 3.0: a major update of the Phenol-Explorer database to incorporate data on the effects of food processing on polyphenol content

Polyphenols are a major class of bioactive phytochemicals whose consumption may play a role in the prevention of a number of chronic diseases such as cardiovascular diseases, type II diabetes and cancers. Phenol-Explorer, launched in 2009, is the only freely available web-based database on the content of polyphenols in food and their in vivo metabolism and pharmacokinetics. Here we report the third release of the database (Phenol-Explorer 3.0), which adds data on the effects of food processing on polyphenol contents in foods. Data on >100 foods, covering 161 polyphenols or groups of polyphenols before and after processing, were collected from 129 peer-reviewed publications and entered into new tables linked to the existing relational design. The effect of processing on polyphenol content is expressed in the form of retention factor coefficients, or the proportion of a given polyphenol retained after processing, adjusted for change in water content. The result is the first database on the effects of food processing on polyphenol content and, following the model initially defined for Phenol-Explorer, all data may be traced back to original sources. The new update will allow polyphenol scientists to more accurately estimate polyphenol exposure from dietary surveys. Database URL: http://www.phenol-explorer.eu

A descriptive study on the surgery and the microbiology of Gustilo type III fractures in an university hospital in Switzerland.

OBJECTIVE: To describe the epidemiology, the surgical treatment, the microbiology, the antibiotic prophylaxis and the outcome of patients with the most severe type of open fractures. METHODS: Retrospective chart reviews of patients with Gustilo type III open fracture admitted to an university hospital in Switzerland between January 2007 and December 2011. The patient's and fracture's characteristics, surgery, antibiotic prophylaxis, and microbiology findings at the initial and at the revision surgery were described. RESULTS: Thirty patients were included (83% male, mean age 41 years). More than half of the patients had polytrauma. In all patients, debridement and stabilization surgery (70% using external fixation) were performed at admission. Soft tissue reconstruction was performed in 87% and in 23% immediate bone graft was performed. Antibiotic prophylaxis were given in all patients for a median duration of 9 days (60% received amoxicillin/clavulanic acid). Positive bacterial culture was found in 53% of the patients at initial surgery and in 88% at revision surgery. At initial and revision surgery, 47% and 88% of the pathogens were amoxicillin/clavulanic acid-resistant. Treatment outcome was favorable in 24 of 30 patients (80%) and in six cases (20%) an amputation had to be performed. None of the patients had chronic bone infection. CONCLUSIONS: Positive cultures were found often in open fractures. Amoxicillin/clavulanic acid which is often mentioned in many guidelines as prophylaxis in open fractures does not cover the most common isolated organisms. The combination of surgery and antibiotic prophylaxis leads to good outcome in Gustilo type III fracture.

Deinking flotation of recycled linerboard for food packaging applications

Brown packaging linerboard, made entirely from recovered pulp, was subjected to deinking flotation for evaluating the possible improvements in its chemical, optical and mechanical properties. The increase in the rate of recovered paper utilisation, along with the tendency towards lower basis weights, in the packaging paper production, has created a growing need for the utilisation of secondary fibers of improved quality. To attain better quality fibers, flotation deinking of brown grades is being considered, along with the addition of primary fibers to recovered paper furnish. Numerous conducted studies, in which the flotation technology was used in the treatment of brown grades, support this idea. Most of them show that the quality of fibers is improved after flotation deinking, resulting in higher mechanical properties of the deinked handsheets and in lower amounts of chemical contaminants. As to food and human health safety, packaging paper has to meet specific requirements, to be classified as suitable for its direct contact with foods. Recycled paper and board may contain many potential contaminants, which, especially in the case of direct food contact, may migrate from packaging materials into foodstuffs. In this work, the linerboard sample selected for deinking was made from recycled fibers not submitted previously to chemical deinking flotation. Therefore, the original sample contained many noncellulosic components, as well as the residues of printing inks. The studied linerboardsample was a type of packaging paper used for contact with food products that are usually peeled before use, e.g. fruits and vegetables. The decrease in the amount of chemical contaminants, after conducting deinking flotation, was evaluated, along with the changes in the mechanical and optical properties of the deinked handsheets. Food contact analysis was done on both the original paper samples and the filter pads and handsheets made before and after deinking flotation. Food contact analysis consisted of migration tests of brightening agents, colorants, PCPs, formaldehydes and metals. Microbiological tests were also performed to determine the possible transfer of antimicrobial constituents