Emulsion versus nanoemulsion : how much is the formulative shift critical for a cosmetic product?

The use of nanoemulsions in cosmetic products has been enlarged in the last decades because of several formulative advantages (e.g., the improved self-life stability, better texture properties). In addition, nanoemulsions seemed to improve the penetration of active ingredients through the human skin, comparing to conventional emulsion. In this contest, the risk of a higher systemic exposure of consumer to active ingredients, due to the ability of nanoemulsion to enhance permeation, results a critical attribute that should be evaluated for assuring the consumer safety. The aim of this work was the evaluation of how an oil-in-water (O/W) nanoemulsion can influence the in vitro skin permeation profiles of two model active ingredients with different polarity (i.e., caffeine and ethyl ximenynate). Preliminarily, since both selected molecules influenced the physical stability of nanoemulsion, formulative studies were carried out to identify the most stable formulation to perform in vitro permeation studies. The overall results demonstrated that nanoemulsions could significantly influence the permeation profiles of molecules as a function of their physicochemical properties. In particular, O/W nanoemulsions significantly improved the permeation profiles of apolar active ingredients in comparison to conventional emulsions, whereas no differences were observable for polar molecules. Considering such findings, it is worth observing that there is room for reconsidering the risk assessment of nanoemulsion-based cosmetic products

Design of in vitro skin permeation studies according to the EMA guideline on quality of transdermal patches

Transdermal patches and medicated plasters are designed to sustain efficacious systemic or loco-regional drug concentrations, respectively. In both cases, drug skin permeation is a critical attribute from the early stage of the pharmaceutical development. In 2014, the EMA introduced the "Guideline on the quality of transdermal patches", in which the importance of equivalence of drug fluxes in in vitro skin permeation study was particularly emphasized to generic or abridged applications for the marketing authorization or manage dossier variations during the product cycle life. Moving from experimental data, this work provides information on the set-up of such studies and the statistical evaluation of obtained fluxes. In particular, the impact of the inter-sample variability on the equivalence assessment was deeply investigated by using formulation pairs containing propranolol, diclofenac or nitroglycerine. The main outputs of the work were attributable to the definition of the acceptability interval and number of replicates to be performed. As an example, the equivalence of two propranolol patches (flux variability lower than 25%) can be assessed using six replicas and a confidence limit within the 0.8-1.25 range (alpha = 0.05; power 90%). In contrast, the equivalence of diclofenac plasters, which exhibit a variability near the 50%, can be demonstrated increasing the number of replicas (i.e., 20 skin samples) for each formulation and widening the acceptance range according to the statistical approach proposed in the work

Glatiramer acetate : a complex drug beyond biologics

Complex drugs may be either biological, if the active ingredients are derived from a biological source, or non-biological, if obtained by chemical synthesis. In both cases, their quality depends considerably on the manufacturing process. In the case of Non Biological Complex Drugs (NBCDs), complexity may arise either from the active substance, as in the case of glatiramer acetate, or from other sources, such as the formulation, as in the case of liposomes. In this paper, the case of glatiramer acetate (GA) - a NBCD relevant for clinical and economic reasons - is considered and the differences between US and EU regulatory approaches to GA marketing authorization are highlighted. Indeed, though US and EU regulatory agencies have chosen a generic approach integrated with additional data the implementation is different in the two jurisdictions. In the US, the additional data required are listed in a product specific guideline and copies of Copaxone\uae have been approved as generics. In the EU, instead regulatory agencies followed a hybrid approach requiring an additional comparative study, and interchangeability policies and substitution schemes have been left to national agencies

Maltodextrins as drying auxiliary agent for the preparation of easily resuspendable nanoparticles

The drying of biodegradable polymeric nanoparticles (NP) is mandatory to improve their physical and chemical stability over time. Spray- or freeze-drying can induce irreversible aggregation of NP and therefore the use of drying auxiliary agents is required. The ability of four grades of maltodextrins differing in dextrose equivalent (DE) (i.e. DE2, DE6, DE12 and DE38) to protect PLGA NP from stresses was studied. High Mw maltodextrins (DE2) was not functional for obtaining an easily resuspendable dried product, since it needs a prolonged time to fully hydrate. Maltodextrins at intermediate DE showed a poor ability to protect NP from irreversible aggregation probably because too sensitive to environmental variation. DE38, which did not alter \u3b6-potential of NP, allowed to obtain an easily resuspendable nanosuspension independently of the drying process. The effectiveness of such material was attributed to the easiness of spray-dry a low viscous solution and to the ability of substitute the water molecules\u2019 hydrogen bonds with NP during freeze-drying

Suspended liquid particle disturbance on laser-induced blast wave and low density distribution

The impurity effect of suspended liquid particles on the laser-induced gas breakdown was experimentally investigated in quiescent gas. The focus of this study is the investigation of the influence of the impurities on the shock wave structure as well as the low density distribution. A 532 nm Nd:YAG laser beam with an 188 mJ/pulse was focused on the chamber filled with suspended liquid particles 0.9 ± 0.63 μm in diameter. Several shock waves are generated by multiple gas breakdowns along the beam path in the breakdown with particles. Four types of shock wave structures can be observed: (1) the dual blast waves with a similar shock radius, (2) the dual blast waves with a large shock radius at the lower breakdown, (3) the dual blast waves with a large shock radius at the upper breakdown, and (4) the triple blast waves. The independent blast waves interact with each other and enhance the shock strength behind the shock front in the lateral direction. The triple blast waves lead to the strongest shock wave in all cases. The shock wave front that propagates toward the opposite laser focal spot impinges on one another, and thereafter a transmitted shock wave (TSW) appears. The TSW interacts with the low density core called a kernel; the kernel then longitudinally expands quickly due to a Richtmyer-Meshkov-like instability. The laser-particle interaction causes an increase in the kernel volume which is approximately five times as large as that in the gas breakdown without particles. In addition, the laser-particle interaction can improve the laser energy efficiency

Subfossil diatoms of Perialpine lakes reveal early lake responses to climate warming and human impact in the 20th century

The majority of Perialpine lakes suffered from nutrient enrichment since the early 1960s because of the demographic growth and the economic boom that followed World War II. However, limnological surveys have remained scattered and irregular for both large and small Perialpine lakes during the early stages of nutrient enrichment, while regular monitoring programs started mainly during the most acute anthropogenic eutrophication or in conjunction with the launching of lake restoration measures. As a result, the early-stage responses of Perialpine lakes to major human-related perturbations occurred during Anthropocene can only be reconstructed based on information preserved in deep lake sediment records. Subfossil diatoms are among the most reliable biological remains in lake sediments and have been extensively used for the reconstruction of the trophic evolution of temperate lakes at secular scale. In this contribution we provide evidence of the capacity of subfossil diatoms to provide information on indirect effects of early global warming occurred in the first half of the 20th century in both large and small Perialpine lakes. We present results of subfossil diatom studies conducted during the last ca. 10 years on sediment cores from a set of large Perialpine, and two additional smaller mid altitude lakes, located on both the northern and southern Alpine slopes. Diatom based environmental reconstructions show that lake biological responses to major changes in lake nutrient availability during the post-war economic development was particularly rapid and coherent in different lake types north and south of the Alps. In addition, these studies reveal that first changes in the diatom species composition occurred already during the first half of the 20th century in several lakes. Although the investigated lakes differ in location, morphology (e.g. altitude, size, depth), and exposition to direct and indirect human impacts, subfossil diatoms first relevant changes mainly occurred between the 1930s and the 1940s. In most of the lakes early diatom changes consist in the rapid substitution of small centric taxa by pennate taxa mainly belonging to the genera Asterionella and Fragilaria. These changes could be interpreted as indirect community response to the first documented climate warming after the end of the Little Ice Age, that mimicked nutrient enrichment effects although being mediated by lake-specific hydrological and thermal dynamics. The interpretation of the observed changes is difficult for some lakes due to the combination of climate related effects with superimposed and simultaneous anthropogenic perturbations that ranged from early eutrophication to hydroelectric exploitation. These results underscore: a) the importance of the paleolimnological approach for complementing and expanding limnological surveys and for predicting future lake ecological trends based on the understanding of past lake responses; b) the potential of subfossil sediment diatoms as a proxy to understand indirect effects of climate change on the planktonic lake biota

LIBS Collection Optics : comparative analysis of different mirror-based configuration

We have evaluated the efficiency of different reflection based optical systems using numerical simulation. We have realized and started testing the most promising one

Effect of the temporal integration on the accuracy of the measured concentration in LIBS measurements

We have developed a simulation program that allows to calculate the plasma emission spectrum of a coal sample in a LIBS experiment. We used the acquired data to evaluate the effect of temporal integration on the accuracy of measured concentration obtained using the calibration free method

Mucoadhesive budesonide formulation for the treatment of eosinophilic esophagitis

Eosinophilic esophagitis (EE) is a chronic immune/antigen-mediated esophageal inflammatory disease for which off-label topical corticosteroids (e.g., budesonide) are widely used in clinic. In general, thickening excipients are mixed with industrial products to improve the residence time of the drug on the esophageal mucosa. The compounding procedures are empirical and the composition is not supported by real physicochemical and technological characterization. The current study aimed to propose a standardized budesonide oral formulation intended to improve the resistance time of the drug on the esophageal mucosa for EE treatment. Different placebo and drug-loaded (0.025% w/w) formulations were prepared by changing the percentage of xanthan gum alone or in ratio 1:1 with guar gum. Both excipients were added in the composition for their mucoadhesive properties. The formulative space was rationalized based on the drug physicochemical stability and the main critical quality attributes of the formulation, e.g., rheological properties, syringeability, mucoadhesiveness and in vitro penetration of budesonide in porcine esophageal tissue. The obtained results demonstrated that gums allowed a prolonged residence time. However, the concentration of the mucoadhesive polymer has to be rationalized appropriately to permit the syringeability of the formulation and, therefore, easy dosing by the patient/caregiver

Differential Epigenetic Changes in the Dorsal Hippocampus of Male and Female SAMP8 Mice: A Preliminary Study

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease characterized by memory loss and cognitive impairment. The causes of the disease are not well understood, as it involves a complex interaction between genetic, environmental, and epigenetic factors. SAMP8 mice have been proposed as a model for studying late-onset AD, since they show age-related learning and memory deficits as well as several features of AD pathogenesis. Epigenetic changes have been described in SAMP8 mice, although sex differences have never been evaluated. Here we used western blot and qPCR analyses to investigate whether epigenetic markers are differentially altered in the dorsal hippocampus, a region important for the regulation of learning and memory, of 9-month-old male and female SAMP8 mice. We found that H3Ac was selectively reduced in male SAMP8 mice compared to male SAMR1 control mice, but not in female mice, whereas H3K27me3 was reduced overall in SAMP8 mice. Moreover, the levels of HDAC2 and JmjD3 were increased, whereas the levels of HDAC4 and Dnmt3a were reduced in SAMP8 mice compared to SAMR1. In addition, levels of HDAC1 were reduced, whereas Utx and Jmjd3 were selectively increased in females compared to males. Although our results are preliminary, they suggest that epigenetic mechanisms in the dorsal hippocampus are differentially regulated in male and female SAMP8 mice