Physicochemical stability of pevonedistat at 50, 100 and 200 µg/mL diluted in 0.9% sodium chloride and at 10 mg/mL in partially used vials.

OBJECTIVES: Pevonedistat is a new cytotoxic used in association with azacitidine for the treatment of acute myeloid leukaemia and high-risk myelodysplastic syndromes. The manufacturer indicates an 18-hour stability after dilution in dextrose 5% or 0.9% sodium chloride (0.9% NaCl) at 2-8°C. No information is given for re-using vials of pevonedistat.Our objectives were to study the physico-chemical stability of 50 and 200 µg/mL pevonedistat diluted in 0.9% NaCl, in glass tubes, 100 µg/mL in 0.9% NaCl in polyolefin infusion bags, and 10 mg/mL partially used vials with a Spike. All preparations were stored at 2-8°C, protected from light. MATERIALS AND METHODS: Due to the limited quantity of pevonedistat available for this study, we prepared test solutions at 50 and 200 µg/mL in glass tubes in a small volume of 20 mL. Inorder to verify the absence of a sorption phenomenon of the molecule onto polyolefin, we prepared two infusion bags at 100 µg/mL. We tested concentrated solution at 10 mg/mL. At each analysis time, we tested three samples of each condition by high performance liquid chromatography (HPLC) coupled with a photodiode array detector. Physical stability was evaluated by a visual and sub-visual inspection. We measured pH at each analysis time. RESULTS: Diluted solutions at 50 and 200 µg/mL in tubes and at 100 mg/mL in infusion bags retained more than 95% of the initial concentration for 14 days, the concentrated solution at 10 mg/mL did so for 7 days. No physical changes were detected visually or sub-visually. We found that pH values remained stable. CONCLUSION: All diluted solutions remained physically and chemically stable for 14 days, the concentrated solution did so for 7 days. No interactions between the polyolefin bag and pevonedistat were demonstrated. This new data allows re-using the concentrated solution of pevonedistat in a commercial glass vial with a Spike, and storing a preparation in case of non-administration.

A new function in the Stabilis database: physical compatibility and incompatibility of injectable drugs to secure Y-site administration.

OBJECTIVES: In intensive care units, the mixing of injectable drugs via Y-site administration is often necessary. However, some mixtures can lead to physical incompatibility or chemical instability. To assist healthcare professionals, several databases such as Stabilis compile compatibility and stability data. The objectives of this study were to update the online database Stabilis by adding physical compatibility data to the website and to characterise the incompatibility data already present in the database by specifying the phenomenon at the origin of the incompatibility and its time of occurrence. METHODS: Bibliographic sources referenced in Stabilis were evaluated using several criteria. After the evaluation, studies were rejected or the data they contain were added to the database. Data entries contained the following information: name of the two injectable drugs involved in the mixture and their concentration if available, the dilution solvent and the phenomenon at the origin of the incompatibility and its time of occurrence for incompatibility data. Three functions of the website were modified, including the 'Y-site compatibility table' function, which allows creation of customised compatibility tables. RESULTS: A total of 1184 bibliographic sources were evaluated, 77.3% (n=915) of which were scientific articles, 20.5% (n=243) were Summaries of Product Characteristics and 2.2% (n=26) were communications in a pharmaceutical congress. After evaluation, 28.9% (n=342) of the sources were rejected. From the 71.1% (n=842) sources selected, 8073 (70.2%) compatibility data entries and 3433 incompatibility data entries (29.8%) were made. With the addition of these data, the database contained compatibility and incompatibility data for 431 injectable drugs. CONCLUSIONS: Since the update, the 'Y-site compatibility table' function has seen its traffic increased by about 66% (∼1500 tables per month compared with ∼2500 tables per month). Stabilis is now more complete to offer significant help to healthcare professionals with their problems of drug stability and compatibility.

Physicochemical stability of cefiderocol, a novel siderophore cephalosporin, in syringes at 62.5 mg/mL for continuous administration in intensive care units.

INTRODUCTION: Cefiderocol is a new siderophore time-dependent antibiotic of last resort. The manufacturer reports a stability of 6 hours for the infusion solution diluted in normal saline (NS) or dextrose 5% in water (D5W) for a concentration between 7.5 and 20 mg/mL. Optimising its effectiveness by continuous infusion is crucial. The aim of this work was to study the physicochemical stability of cefiderocol diluted in NS or D5W in polypropylene syringes for 48 hours at a concentration of 62.5 mg/mL stored at room temperature, protected or not from light. MATERIALS AND METHODS: Three preparations for each condition were performed. At each time of the analysis, one sample for each preparation was analysed in triplicate by a validated high performance liquid chromatography method coupled to a photodiode array detector at 260 nm. Particle contamination, absorbance measurement, visual inspection and pH measurement were assessed. The limit of stability was set at 90% of the initial concentration, without physical modification. RESULTS: The linearity was validated with an R² of 0.9999. The coefficients of variation for repeatability and intermediate precision were less than 2%. In NS and D5W, cefiderocol retained more than 90% of the initial concentration after 12 hours in syringes, exposed or not to light. Two degradation products (nos 2 and 11, observed during forced degradation) were detected during the stability study. The absorbance at 410 nm increased progressively, regardless of the storage conditions. The particulate contamination test met the specifications of the container. pH values were all between 5.22 and 5.32. No visual changes were detected. CONCLUSION: In polypropylene syringes, cefiderocol 62.5 mg/mL (3 g in 48 mL) diluted in NS or D5W was stable for 12 hours at room temperature. These new data allow the use of cefiderocol in continuous infusion.

Food-inspired innovations to improve the stability of active pharmaceutical ingredients.

Food-processing and pharmaceutical industries share a lot of stability issues against the same physical, chemical, and microbiological phenomena. They also share some solutions to improve the stability as the use of preservatives and packaging. Ecological concerns lead to the development of tremendous innovations in food. Some of these innovations could also be beneficial in the pharmaceutical domain. The objective of this review is to evaluate the potential application of these findings in the pharmaceutical field and the main limits in terms of toxicity, environmental, economic and regulatory issues. The principal factors influencing the shelf-life were highlighted through the description of the stability studies usually performed in the pharmaceutical industry (according to European guidelines). To counter those factors, different solutions are currently available as preservatives and specific packaging. They were described and debated with an overview of recent food innovations in each field. The limits of the current solutions in the pharmaceutical field and the innovation in the food field have inspired a critical pharmaceutical outlook. The active and intelligent packaging for active pharmaceutical ingredients of the future is imagined.

Stability Studies of 16 Antibiotics for Continuous Infusion in Intensive Care Units and for Performing Outpatient Parenteral Antimicrobial Therapy.

The use of continuous infusion to improve the therapeutic efficacy of time-dependent antibiotics has been demonstrated. There is still a lack of data to safely perform these continuous infusions. The objectives in this study were to evaluate the stability by using stability-indicating methods (High-Performance Liquid Chromatography) of 16 antibiotics in concentrated solutions, especially for administration in intensive care units and solutions in elastomeric diffusers at 37 °C for outpatient parenteral antimicrobial therapy. The solutions were considered stable if the percentage of the drug was ≥90%, and the colour and clearness remained unchanged. In syringes, the stability data vary from 4 to 8 h (h) for meropenem in Dextrose 5% (D5W) and Normal Saline (NS), respectively, 6 h for cefotaxime, 12 h for cefoxitin, and 24 h for aztreonam, cefazolin, cefepime, cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam in NS and D5W, and in water for injection for cloxacillin. A stability period of 48 h has been validated for vancomycin (D5W), aztreonam, and piperacillin/tazobactam. Cefoxitin, cefazolin, cefepime, cefotaxime, cloxacillin, and piperacillin are unstable for diffuser administration. In diffusers, stability times vary from 6 h for cefiderocol, 8 h for ceftazidime, 12 h for ceftazidime/avibactam and ceftolozane/tazobactam (NS), 24 h for temocillin (NS) and piperacillin/tazobactam (D5W), up to 48 h for aztreonam and vancomycin. Solutions stored at 37 °C are less stable and allow the administration of seven antibiotics using diffusers.

High concentrated etoposide solutions, additional physical stability data in dextrose 5.

OBJECTIVES: According to the manufacturers, the concentration of etoposide solutions should not exceed 0.4 mg/mL due to a risk of precipitation. Stability studies at higher concentrations were conducted and notably demonstrated 28 day stability up to 1.75 mg/mL for etoposide solutions in 5% dextrose (D5W). Nevertheless, colleagues report precipitation even at 0.4 mg/mL in their daily practice. The objective of this work was to reassess the physical stability of highly concentrated etoposide solutions in D5W (1.2 mg/mL), over a large number of preparations and under different manufacturing processes. METHODS: To study the impact of manufacturing process, etoposide was taken with a spike or a needle and injected in three types of D5W containers (Easyflex, Viaflo and Ecoflac). Forty preparations were made for each container. For half of the preparations, a homogenisation was performed by a syringe rinse. Physical stability was realised by two examiners, with a visual examination searching for the appearance of a precipitate, daily during the first week, then twice a week until day 56. RESULTS: Hundred and eighteen solutions were clear and colourless. Precipitates were observed for two solutions: one in an Easyflex bag on day 4 and one in an Ecoflac container on day 35. CONCLUSIONS: The physical stability at 1.2 mg/mL in D5W remains validated. Precipitations are rare and concern less than 2% of preparations. The appearance of a precipitate does not seem to be correlated to the kind of container or manufacturing process. A rinse was performed for these two solutions to assess a mechanical pressure effect more important on the solution, which could lead to a higher risk of precipitations. However, this is not observed in our daily practice, especially at lower concentrated solutions. We only recommend using an administration set with an in-line micro-filter as a precaution in case of precipitations.

Physicochemical stability of nefopam and nefopam/droperidol solutions in polypropylene syringes for intensive care units.

Introduction: Nefopam has been reported to be effective in postoperative pain control with an opioid-sparing effect, but the use of nefopam can lead to nausea and vomiting. To prevent these side effects, droperidol can be mixed with nefopam. In intensive care units, high concentrations of nefopam and droperidol in syringes can be used with a continuous flow. Objectives: The first objective of this work was to study the physicochemical stability of a nefopam solution 2.5 mg/mL diluted in NaCl 0.9% in polypropylene syringes immediately after preparation and after 6, 24 and 48 hours at room temperature. The second objective was to study the physicochemical stability of mixtures of nefopam 2.5 mg/mL and droperidol 52 µg/mL diluted in NaCl 0.9% in polypropylene syringes at room temperature over 48 hours. Materials and methods: Three syringes for each condition were prepared. For each time of analysis, three samples for each syringe were prepared and analysed by high performance liquid chromatography coupled to photodiode array detection. The method was validated according to the International Conference on Harmonisation Q2(R1). Physical stability was evaluated by visual and subvisual inspection (turbidimetry by UV spectrophotometry). pH values were measured at each time of analysis. Results: Solutions of nefopam at 2.5 mg/mL and the mixture of nefopam 2.5 mg/mL with droperidol 52 µg/mL, diluted in NaCl 0.9%, without protection from light, retained more than 90% of the initial concentration after 48 hours storage at 20-25°C. No modification in visual or subvisual evaluation and pH values were observed. Conclusion: Nefopam solutions at 2.5 mg/mL and the mixture of nefopam 2.5 mg/mL with droperidol 52 µg/mL diluted in NaCl 0.9% were stable over a period of 48 hours at room temperature. These stability data provide additional knowledge to assist intensive care services in daily practice.

Physicochemical stability of an admixture of lidocaine and ketamine in polypropylene syringe used in opioid-free anaesthesia.

Objectives: Opioid-free anaesthesia is a treatment strategy of pain management based on the use of drugs such as lidocaine, ketamine and dexmedetomidine that do not interact significantly with opioid receptors. In particular, these drugs are used by anaesthesiologists to ensure adequate levels of analgesia during surgical procedures for burn patients such as daily wound dressings and graft surgeries. Furthermore, for hypothermia prevention and wound-healing purposes, ambient temperature must be kept high for these patients, usually between 27°C and 30°C. To facilitate the use of this technique, clinicians want to mix lidocaine and ketamine in the same syringe. No stability data is available to determine the feasibility of this admixture and at this temperature. The objective was to study the physicochemical stability of lidocaine 20 mg/mL with ketamine 2.5 mg/mL diluted with 0.9% sodium chloride (0.9% NaCl) stored at 28°C in polypropylene syringe for 48 hours. Methods: Physical stability was evaluated by visual examination and by measuring turbidity with a spectrophotometer. Chemical stability was determined after preparation and after 6, 24 and 48 hours of conservation with a high performance liquid chromatography and pH measurements. The method was validated according to International Conference on Harmonisation Q2(R1) guidelines. Results: Both lidocaine (99.98%±1.44%) and ketamine (100.70%±0.95%) retained more than 95% of their initial concentration after 48 hours storage. pH measurements remained stable over the course of the study (less than 0.21 point of variation). No signs of physical instability were observed after visual and subvisual inspections. Conclusions: The physicochemical stability of lidocaine 20 mg/mL and ketamine 2.5 mg/mL diluted with 0.9% NaCl in a polypropylene syringe stored at 28°C protected from light was demonstrated for 48 hours. This infusion technique is therefore feasible from a pharmaceutical point of view in burn-unit settings.

Physicochemical stability of etoposide diluted at range concentrations between 0.38 and 1.75 mg/mL in polyolefin bags.

Introduction: According to the manufacturers, the diluted solution of etoposide should not exceed 0.4 mg/mL because precipitation may occur. For high doses or for patients requiring fluid restrictions, etoposide phosphate may be an option but shortages occurs frequently. The objective of this work was to study the stability of etoposide solutions between 0.38 and 1.75 mg/mL, diluted in 0.9% sodium chloride (0.9% NaCl) or 5% glucose (G5%) in polyolefin bags, stored at 25°C and between 2°C to 8°C, in a 61-day period. This study also observed the impact of an infusion pump on the physical and chemical stability of etoposide solutions. Materials and method: Chemical stability was analysed at days 0, 9, 16, 21, 28 and 61 by high-performance liquid chromatography. Physical stability was evaluated by visual and subvisual inspection. The action of an infusion pump on solutions was evaluated to verify the impact of the mechanical pumping action on the etoposide solutions. This investigation was performed at day 61, at the end of the study. Results: Etoposide solutions diluted at 0.38, 0.74 and 1.26 mg/mL in G5% and stored at 25°C were stable for 61 days and at 1.75 mg/mL for 28 days. In 0.9% NaCl, etoposide was less stable, with more precipitations observed. The action of an infusion pump has not caused any physical modifications. Conclusion: Storage at 25°C and G5% as diluent are recommended for etoposide high concentration with 61-day stability up to a concentration of 1.26 mg/mL and 28-day stability up to a concentration of 1.75 mg/mL. As a precaution, the use of an administration set with an in-line micro-filter is nevertheless recommended. Storage at 2°C to 8°C and the use of 0.9% NaCl increase the risk of precipitation.

Physicochemical Stability of Vancomycin at High Concentrations in Polypropylene Syringes.

BACKGROUND: In severe infections, high-concentration vancomycin may be administered by continuous infusion. The dosage of vancomycin may reach 60 mg/kg per day. OBJECTIVES: To study the feasibility of preparing high-concentration vancomycin solutions (40 to 83.3 mg/mL), to study the effect of an electric syringe pump on the physical stability of high-concentration vancomycin, and to study the stability of vancomycin 62.5 and 83.3 mg/mL in 0.9% sodium chloride (0.9% NaCl) or 5% dextrose in water (D5W) with storage up to 48 h at room temperature. METHODS: The following sets of syringes were prepared: (1) 4 syringes of vancomycin in 0.9% NaCl for each of 5 concentrations between 40 and 83.3 mg/mL (total 20 syringes); (2) 6 syringes at 83.3 mg/mL in 0.9% NaCl and 6 syringes at 83.3 mg/mL in D5W; and (3) 30 syringes at 83.3 mg/mL in D5W. Visual inspection was performed for all 3 syringe sets, and subvisual inspection for sets 1 and 2 (for periods of 24 h for set 1 and 48 h for sets 2 and 3). One syringe of vancomycin 83.3 mg/mL with each solvent was inserted into an electric syringe pump, and samples from the infusion line and collected after transit through the pump were inspected visually. Chemical stability was evaluated by high-performance liquid chromatography, and physical stability, pH, and osmolality were investigated. RESULTS: For all sets of syringes, no physical modification was observed over time, nor were any changes observed after transit through the electric syringe pump. In 0.9% NaCl, vancomycin 62.5 and 83.3 mg/mL retained more than 90% of the initial concentration after 48 and 24 h, respectively; however, for the 83.3 mg/mL solution, precipitate was visible after 48 h. In D5W, vancomycin at 62.5 and 83.3 mg/mL retained more than 90% of the initial concentration after 48 h. CONCLUSION: It was feasible to prepare high-concentration solutions of vancomycin. The electric syringe pump did not cause any precipitation. Vancomycin in D5W at 62.5 and 83.3 mg/mL was stable over 48 h at room temperature. Precipitation occurred in 0.9% NaCl. D5W is therefore recommended as the solvent for this drug.

CONTEXTE: En cas d'infection grave, de la vancomycine à forte concentration peut être administrée par perfusion continue à une dose pouvant atteindre 60 mg/kg par jour. OBJECTIFS: Mener une étude de faisabilité portant sur la préparation de solutions de vancomycine à forte concentration (de 40 à 83,3 mg/mL); étudier l'effet d'un pousse-seringue électrique sur la stabilité physique de la vancomycine à forte concentration; et étudier la stabilité de la vancomycine (62,5 et 83,3 mg/mL) dans une solution de chlorure de sodium à 0,9 % (NaCl à 0,9 %) ou dans une solution aqueuse de dextrose à 5 % (D5W) après 48 h à la température ambiante. MÉTHODES: Trois ensembles de seringues ont été préparés : (1) quatre seringues de vancomycine dans une solution de NaCl à 0,9 %, à chacune des cinq concentrations comprises entre 40 et 83,3 mg/mL (20 seringues au total); (2) six seringues à 83,3 mg/mL dans une solution de NaCl à 0,9 % et six seringues à 83,3 mg/mL dans une solution de D5W; et (3) 30 seringues à 83,3 mg/mL dans une solution de D5W. Une inspection visuelle des trois ensembles de seringues et une inspection « sous-visuelle ¼ des ensembles 1 et 2 ont eu lieu (période de 24 h pour l'ensemble 1 et de 48 h pour les ensembles 2 et 3). Une seringue contenant de la vancomycine à 83,3 mg/mL mélangée à chaque solvant a été insérée dans un pousse-seringue électrique, et les échantillons prélevés dans le tube de perfusion et ceux recueillis après leur passage dans la pompe ont été inspectés visuellement. La stabilité chimique a été évaluée par chromatographie liquide à haute performance et la stabilité physique, le pH ainsi que l'osmolalité ont eux aussi été étudiés. RÉSULTATS: Les trois ensembles de seringues n'ont présenté aucune modification physique avec le temps. Aucun changement n'a non plus été observé après le passage dans le pousse-seringue électrique. Dans la solution de NaCl à 0,9 %, la vancomycine à 62,5 et à 83,3 mg/mL a conservé plus de 90 % de sa concentration initiale respectivement après 48 et 24 h. Cependant, le précipité de la solution à 83,3 mg/mL était visible après 48 h. Dans la solution de D5W, la vancomycine à 62,5 et à 83,3 mg/mL a conservé plus de 90 % de sa concentration initiale après 48 h. CONCLUSION: La préparation de solutions de vancomycine à forte concentration est faisable. Le pousse-seringue électrique n'a pas causé de précipitation. La vancomycine dans la solution de D5W à 62,5 et à 83,3 mg/mL est restée stable pendant plus de 48 h à la température ambiante. Les précipitations se sont produites dans les solutions de NaCl à 0,9 %. On recommande donc la solution de D5W comme solvant pour ce médicament.

Ifosfamide-induced encephalopathy: Brand-name (HOLOXAN®) vs generic formulation (IFOSFAMIDE EG®).

WHAT IS KNOWN AND OBJECTIVE: Two forms of ifosfamide are commercially available in France: HOLOXAN® (brand-name drug) and IFOSFAMIDE EG® (generic drug). Following the marketing launch of the generic drug, there has been a significant increase in cases of ifosfamide-induced encephalopathy reported in France. Our objective is to compare the incidence of ifosfamide-induced encephalopathy in adult patients treated with HOLOXAN® or IFOSFAMIDE EG®. METHODS: This is a retrospective study of adult patients treated with ifosfamide in two medical centers from 2013 to 2017, with data analysed from medical records. Comparisons of patients were made, according to the formulation used and according to the occurrence of ifosfamide-induced encephalopathy. The groups of patients were compared using a chi-square or Fisher's exact test for qualitative parameters and a Wilcoxon test for quantitative parameters. To include confounding factors in the analysis of the impact of drug formulation on the occurrence of ifosfamide-induced encephalopathy, a generalized linear model was performed with the occurrence of ifosfamide-induced encephalopathy as the dependent parameter, and the formulation and the confounding factors as explanatory parameters. RESULTS AND DISCUSSION: A total of 191 patients were included: 103 patients received HOLOXAN® (53.9%) and 88 patients received IFOSFAMIDE EG® (46.1%). In the HOLOXAN® group, the median infusion time was higher (12 hours vs 3h, P < 0.001) and aprepitant was administered more frequently (78.6% vs 69.7%, P < 0.001) than for the IFOSFAMIDE EG® group. Ifosfamide-induced encephalopathy occurred in 11 patients (5.8%, CI 95% [2.9%, 10.0%]). In the ifosfamide-induced encephalopathy group, median infusion time was higher (12 hours [12; 24] vs 3 hours [2; 12] P < 0.001) and a poor performance status was more frequent (54.5% vs 13.9%, P = 0.002) than in the group without ifosfamide-induced encephalopathy. The frequency of ifosfamide-induced encephalopathy in the HOLOXAN® group was 1.9% (2/103) against 10.2% (9/88) in the IFOSFAMIDE EG® group (P = 0.014). Multivariate analysis revealed that treatment with IFOSFAMIDE EG® resulted in significantly more ifosfamide-induced encephalopathies compared to HOLOXAN® (OR and CI 95%:7.4 [1.4; 39.5], P = 0.018). We identified two other risk factors for ifosfamide-induced encephalopathy: long-term infusion and a performance status of two or higher. WHAT IS NEW AND CONCLUSION: The formation of chloroethylamine in solution could be the cause of more frequent ifosfamide-induced encephalopathies with IFOSFAMIDE EG® compared to HOLOXAN®. Application of these data could help in the choice of ifosfamide formulation in adult patients to decrease the risk of ifosfamide-induced encephalopathy, and more specifically for patients with risk factors.

Total Internal Reflection Accounts for the Bright Color of the Saharan Silver Ant.

The Saharan silver ant Cataglyphis bombycina is one of the terrestrial living organisms best adapted to tolerate high temperatures. It has recently been shown that the hairs covering the ant's dorsal body part are responsible for its silvery appearance. The hairs have a triangular cross-section with two corrugated surfaces allowing a high optical reflection in the visible and near-infrared (NIR) range of the spectrum while maximizing heat emissivity in the mid-infrared (MIR). Those two effects account for remarkable thermoregulatory properties, enabling the ant to maintain a lower thermal steady state and to cope with the high temperature of its natural habitat. In this paper, we further investigate how geometrical optical and high reflection properties account for the bright silver color of C. bombycina. Using optical ray-tracing models and attenuated total reflection (ATR) experiments, we show that, for a large range of incidence angles, total internal reflection (TIR) conditions are satisfied on the basal face of each hair for light entering and exiting through its upper faces. The reflection properties of the hairs are further enhanced by the presence of the corrugated surface, giving them an almost total specular reflectance for most incidence angles. We also show that hairs provide an almost 10-fold increase in light reflection, and we confirm experimentally that they are responsible for a lower internal body temperature under incident sunlight. Overall, this study improves our understanding of the optical mechanisms responsible for the silver color of C. bombycina and the remarkable thermoregulatory properties of the hair coat covering the ant's body.

Radiative contribution to thermal conductance in animal furs and other woolly insulators.

This paper deals with radiation's contribution to thermal insulation. The mechanism by which a stack of absorbers limits radiative heat transfer is examined in detail both for black-body shields and grey-body shields. It shows that radiation energy transfer rates should be much faster than conduction rates. It demonstrates that, for opaque screens, increased reflectivity will dramatically reduce the rate of heat transfer, improving thermal insulation. This simple model is thought to contribute to the understanding of how animal furs, human clothes, rockwool insulators, thermo-protective containers, and many other passive energy-saving devices operate.

Method for modeling additive color effect in photonic polycrystals with form anisotropic elements: the case of Entimus imperialis weevil.

The calculation of the reflectance of photonic crystals having form-birefringent anisotropic elements in the crystal unit cell, such as cylinders, often turns out to be problematic, especially when the reflectance spectrum has to be computed according to different crystal orientations as in polycrystals for instance. The method we propose here solves this problem in the specific case of photonic crystals whose periodicities are such that there are no diffraction orders except Bragg reflection in the visible range. For a given crystal orientation, the crystal is sliced into layers and the periodic spatial variations of the dielectric function ε are homogenized. Thanks to that homogenization, the calculation can be performed using standard thin film computation codes. In order to demonstrate the usefulness of our method, we applied it to the case of a natural photonic polycrystal found on the cuticle of Entimus imperialis weevil which is a remarkable example of additive color effect. Although each photonic crystal grain of the polycrystal produces a single bright iridescent color, a non-iridescent green matt coloration is perceived by the human eye due to multiscale averaging effects.

Cylindrical Bragg mirrors on leg segments of the male Bolivian blueleg tarantula Pamphobeteus antinous (Theraphosidae).

The large male tarantula Pamphobeteus antinous is easily recognized at the presence of blue-violet iridescent bristles on some of the segments of its legs and pedipalps. The optical properties of these colored appendages have been measured and the internal geometrical structure of the bristles have been investigated. The coloration is shown to be caused by a curved coaxial multilayer which acts as a "cylindrical Bragg mirror".

Improved light extraction in the bioluminescent lantern of a Photuris firefly (Lampyridae).

A common problem of light sources emitting from an homogeneous high-refractive index medium into air is the loss of photons by total internal reflection. Bioluminescent organisms, as well as artificial devices, have to face this problem. It is expected that life, with its mechanisms for evolution, would have selected appropriate optical structures to get around this problem, at least partially. The morphology of the lantern of a specific firefly in the genus Photuris has been examined. The optical properties of the different parts of this lantern have been modelled, in order to determine their positive or adverse effect with regard to the global light extraction. We conclude that the most efficient pieces of the lantern structure are the misfit of the external scales (which produce abrupt roughness in air) and the lowering of the refractive index at the level of the cluster of photocytes, where the bioluminescent production takes place.

Optimal overlayer inspired by Photuris firefly improves light-extraction efficiency of existing light-emitting diodes.

In this paper the design, fabrication and characterization of a bioinspired overlayer deposited on a GaN LED is described. The purpose of this overlayer is to improve light extraction into air from the diode's high refractive-index active material. The layer design is inspired by the microstructure found in the firefly Photuris sp. The actual dimensions and material composition have been optimized to take into account the high refractive index of the GaN diode stack. This two-dimensional pattern contrasts other designs by its unusual profile, its larger dimensions and the fact that it can be tailored to an existing diode design rather than requiring a complete redesign of the diode geometry. The gain of light extraction reaches values up to 55% with respect to the reference unprocessed LED.

Bi-functional photonic structure in the Papilio nireus (Papilionidae): modeling by scattering-matrix optical simulations.

Scales of the Papilio nireus combine fluorophores confined in a natural photonic structure. By means of numerical simulations based on the scattering-matrix formalism, we reveal the bi-functional optical role of this peculiar architecture. Two aspects are considered: the absorption of an incident light flux and the emission of another luminous flux. First, results highlight a light trapping effect and a light absorption increase in the ultraviolet, visible and near infrared ranges. Then, results highlight an enhanced fluorescence occurring in the spatial as well as in the frequency domain. This observation could be of great interest to design new optical devices.

Photonic polycrystal in the greenish-white scales of the African longhorn beetle Prosopocera lactator (Cerambycidae).

Three-dimensional photonic-crystal grains were found in the scales of the longhorn beetle Prosopocera lactator (Cerambycidae). The local geometric structure can be described as a face-centered-cubic array of spheres, connected by short rods, reminiscent of the "ball-and-stick" models used by solid-state chemists to visualize atomic structures. Based on scanning electron microscopy, x-ray nanotomography, optical measurements, photonic band-structure calculations, and computer simulations of the reflectance, the desaturated greenish coloration is shown to arise from the observed photonic polycrystalline structure. X-ray nanotomography is revealed as a very promising tool for photonic-crystal morphology studies.