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Serena Logrippo,1,2 Giovanna Ricci,3 Matteo Sestili,4 Marco Cespi,2 Letizia Ferrara,4 Giovanni F Palmieri,2 Roberta Ganzetti,4 Giulia Bonacucina,2 Paolo Blasi2 1School of Advanced Studies, 2School of Pharmacy, 3School of Law, University of Camerino, Camerino, 4Italian National Research Centers on Ageing (INRCA), Ancona, Italy Abstract: Demographic indicators forecast that by 2050, the elderly will account for about one-third of the global population. Geriatric patients require a large number of medicines, and in most cases, these products are administered as solid oral solid dosage forms, as they are by far the most common formulations on the market. However, this population tends to suffer difficulties with swallowing. Caregivers in hospital geriatric units routinely compound in solid oral dosage forms for dysphagic patients by crushing the tablets or opening the capsules to facilitate administration. The manipulation of a tablet or a capsule, if not clearly indicated in the product labeling, is an off-label use of the medicine, and must be supported by documented scientific evidence and requires the patient’s informed consent. Compounding of marketed products has been recognized as being responsible for an increased number of adverse events and medical errors. Since extemporaneous compounding is the rule and not the exception in geriatrics departments, the seriousness and scope of issues caused by this daily practice are probably underestimated. In this article, the potential problems associated with the manipulation of authorized solid oral dosage forms are discussed. Keywords: geriatric medicine, dysphagia, compounding, modified-release formulations, gastrointestinal tract toxicity

Karim S Shalaby,1 Mahmoud E Soliman,1 Luca Casettari,2 Giulia Bonacucina,3 Marco Cespi,3 Giovanni F Palmieri,3 Omaima A Sammour,1 Abdelhameed A El Shamy1,† 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt; 2Department of Biomolecular Sciences, School of Pharmacy, University of Urbino, Urbino, Italy; 3School of Pharmacy, University of Camerino, Camerino, Italy †Abdel Hameed El-Shamy passed away on August 25, 2013 Abstract: In this study, di- and triblock copolymers based on polyethylene glycol and polylactide were synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance and gel permeation chromatography. Nanoparticles containing noscapine were prepared from these biodegradable and biocompatible copolymers using the nanoprecipitation method. The prepared nanoparticles were characterized for size and drug entrapment efficiency, and their morphology and size were checked by transmission electron microscopy imaging. Artificial neural networks were constructed and tested for their ability to predict particle size and entrapment efficiency of noscapine within the formed nanoparticles using different factors utilized in the preparation step, namely polymer molecular weight, ratio of polymer to drug, and number of blocks that make up the polymer. Using these networks, it was found that the polymer molecular weight has the greatest effect on particle size. On the other hand, polymer to drug ratio was found to be the most influential factor on drug entrapment efficiency. This study demonstrated the ability of artificial neural networks to predict not only the particle size of the formed nanoparticles but also the drug entrapment efficiency. This may have a great impact on the design of polyethylene glycol and polylactide-based copolymers, and can be used to customize the required target formulations. Keywords: noscapine, polyethylene glycol (PEG), polylactide (PLA), biodegradable nanoparticles, artificial neural networks (ANNs)

One interesting field of research in the view of developing novel surfactants for pharmaceutical and cosmetic applications is the design of amphiphiles showing further bioactive properties in addition to those commonly displayed by surface-active compounds. We propose here the chemical synthesis, and characterization of 1-o-tolyl alkyl biguanide derivatives, having different lengths of the hydrocarbon chain (C3, C6, and C10), and showing surface active and antibacterial/disinfectant activities toward both Gram-positive and Gram-negative bacteria. Both surface active properties in terms of critical micelle concentration (CMC) and surface tension at CMC (γCMC), as well as the antimicrobial activity in terms of minimum inhibitory concentrations (MICs), were strongly dependent on the length of the hydrocarbon chain. Particularly, the C6 and C10 derivatives have a good ability to decrease surface tension (γCMC <40 mN/m) at low concentrations (CMC < 12 mM) and a satisfactory antibacterial effect (MIC values between 0.230 and 0.012 mM against S. aureus strains and between 0.910 and 0.190 against P.aeruginosa strains). Interestingly, these compounds showed a disinfectant activity at the tested concentrations that was comparable to that of the reference compound chlorhexidine digluconate. All these results support the possible use of these amphiphilic compounds as antibacterial agents and disinfectants in pharmaceutical or cosmetic formulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Green technologies based on microwaves have been developed by the food industry to produce organoleptically acceptable fruit juices without preliminary processing. Microwave irradiation coupled with hydrodiffusion and gravity (MHG) combines microwave heating with the earth's gravity, allowing the collection of hydrophilic substances released from the irradiated matrix. To the best of our knowledge, MHG extraction has never been experimented to produce pomegranate juice. In this work, we have evaluated it as a potential alternative to the conventional squeezing. A central composite design study (CCD) allowed the selection of the best extractive conditions (irradiation power and extraction time) to obtain a pomegranate juice with higher yield, polyphenol (e.g., catechin and delphinidin-3,5-glucoside) content, and related bioactivities (antioxidant and antidiabetic) than the one obtained by squeezing while maintaining the chemical-physical properties. Thus, this technique appears to be a functional alternative to producing high value pomegranate juice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The coating process for solid dosage forms is widely used in the pharmaceutical industry but presents challenges for small-scale production, needed in personalized medicine and clinical or galenic settings. This study aimed to evaluate immersion coating, a cost-effective small-scale method, for enteric-coated gelatin capsules using standard equipment. Two enteric coating polymers and different polymer concentrations were tested, along with API solubility. Results were compared with commercially available enteric capsule shells. Successful preparation of enteric coating capsules via immersion necessitates a comprehensive grasp of API and enteric polymer behavior. However, utilizing commercially available enteric capsule shells does not guarantee ease or robustness, as their efficacy hinges on the attributes of the active ingredient and excipients. Notably, coating with Eudragit S100 stands out for its superior process robustness, requiring minimal or no development time, thus representing the best option for small-scale enteric capsule production.

Background: Compounding solid oral dosage forms into liquid preparations is a common practice for administering drug therapy to patients with swallowing difficulties. This is particularly relevant for those on enteral nutrition, where factors such as the administration procedure and co-administration of enteral nutrition play crucial roles in effective drug delivery. Due to the limited studies focused on this practice, the impact of co-administered nutrition remains unclear., Methods: Pravastatin tablets were compounded into two liquid formulations and administered through three independent tubes for ten cycles. The drug amount was quantified upstream and downstream of the tubes both with and without different (fiber content) nutritional boluses., Results: The compounding procedure did not lower the drug amount with respect to the original tablets. However, when the liquid formulation was pumped through the tubes, a statistically significant reduction in the pravastatin administered (between 4.6% and 11.3%) was observed. The co-administration of different nutritional boluses or the compounding procedure did not affect the general results., Conclusions: Pravastatin loss appears unavoidable when administered via the enteral tube. Although, in this case, the loss was of limited clinical relevance, it is important not to underestimate this phenomenon, especially with drugs having a narrow therapeutic index.

The quality parameters of cappuccinos prepared with pasteurized milk or ultra-high-temperature milk steam-injected at different temperatures by a professional coffee machine have been assessed. In particular, the protein profile, the content of vitamins and lactose, the lipid peroxidation process, and the involvement of milk proteins in the foam formation were evaluated. The nutritional quality of milk seems not affected by the steam injection treatment carried out at a temperature of 60-65 °C, but at higher temperatures a decrement of lactoperoxidase, vitamin B6 and folic acid was observed. The milk used in cappuccino preparation is very important: pasteurized milk can form a more consistent and lasting foam with respect to ultra-high-temperature milk because of the presence of β-lactoglobulin and lactoferrin, both playing an important role in the foam formation and stability. This work would provide additional information to the coffee industry for the preparation of high nutritional and organoleptic quality cappuccinos., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Saquinavir mesylate (SQV) is a protease inhibitor commonly employed for the treatment of human immunodeficiency virus-1 infection. It is generally administered orally as tablets in combination with other antiviral drugs. Another promising route of administration can be represented by the vaginal one through topically applied formulations. This delivery can reduce the first-pass effect in the case of systemic drug adsorption or prevent HIV infection. We propose the formulation of a Carbopol® 974 (C974) hydrogel containing biodegradable mPEG-PL(L)GA nanoparticles (NPs) for the vaginal delivery of SQV, intended both as a prevention and a therapeutic strategy. mPEG-PL(L)GA NPs were incorporated into the C974 polymeric matrix, leading to a reduction of the hydrogel consistency dependent on NPs and C974 concentrations. Despite the moderate drug loading into NPs, the presence of the NPs had an impact on the in vitro release of the drug from the hydrogel at pH 5.5 using immersion cells. A higher amount of the drug was released, probably due to the effect of NPs in promoting the incorporation of the drug into the hydrogel at a high SQV dose. These findings can be useful for the development of topically applied hydrogels for SQV delivery, possibly having improved in vivo therapeutic outcomes., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Alopecia is a pathological and multifactorial condition characterised by an altered hair growth cycle and ascribed to different pathogenic causes. Cell energetic imbalances in hair follicles occurring in this disorder could lead to the production of some "metabolic wastes", including squalene and lactic acid, which could be involved in the clinically observed sheath damage. The aim of this work was the extraction and analytical quantification of squalene and lactic acid from hair bulbs of subjects with clinical alopecia in comparison with controls, using HPLC-DAD and HPLC-MS techniques. The analytical quantification was performed after a preliminary observation through a polarised optical microscope to assess sheath damage and morphological alterations in the cases group. A significantly larger amount of squalene was quantified only in subjects affected by alopecia ( n = 31) and with evident damage to hair sheaths. For lactic acid, no statistically significant differences were found between cases ( n = 21) and controls ( n = 21) under the experimental conditions used. Therefore, the obtained results suggest that squalene can represent a metabolic and a pathogenic marker for some alopecia conditions.

Industrial hemp ( Cannabis sativa L.), due to its bioactive compounds (terpenes and cannabinoids), has gained increasing interest in different fields, including for medical purposes. The evaluation of the safety profile of hemp essential oil (EO) and its encapsulated form (nanoemulsion, NE) is a relevant aspect for potential therapeutic applications. This study aimed to evaluate the toxicological effect of hemp EOs and NEs from cultivars Carmagnola CS and Uso 31 on three cell lines selected as models for topical and inhalant administration, by evaluating the cytotoxicity and the cytokine expression profiles. Results show that EOs and their NEs have comparable cytotoxicity, if considering the quantity of EO present in the NE. Moreover, cells treated with EOs and NEs showed, in most of the cases, lower levels of proinflammatory cytokines compared to Etoposide used as a positive control, and the basal level of inflammatory cytokines was not altered, suggesting a safety profile of hemp EOs and their NEs to support their use for medical applications.

Lubricants are excipients used in tablet formulations to reduce friction and adhesion forces within the die or on the punches surface during the manufacturing process. Despite these excipients are always required for the tablets production, their amount must be carefully evaluated since lubricants can negatively impact on mechanical strength, disintegration and dissolution behavior of solid dosage forms. Alternative compounds have been suggested to overcome the issues of conventional lubricants and sodium lauryl sulfate (SDS) is one of the most promising one. Despite SDS has been object of several investigations, a definitive conclusion on its effectiveness cannot still be drawn. Particularly, its efficacy on tablets disaggregation and API dissolution is still unclear. Here, the effect of SDS on all the relevant features of tablets and tableting process has been evaluated on immediate release hydrophobic tablets formulations in comparison with conventional lubricants. The results of this investigation are quite outspoken: SDS has a low lubricant power while it determines only a limited improvement on tablets hardness. It greatly improves the tablets wettability but only on model formulations, the presence of superdisintegrants resets its effectiveness and any possible effect on tablets disaggregation. None of the tested formulations showed improvement on the API dissolution rate., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Rosehips, Rosa canina L. (Rosaceae family), have been used for a long time for their beneficial effects on health, and they are largely exploited in the food and nutraceutical supplement sectors. The aim of this work was to apply and optimize for the first time the microwave hydrodiffusion and gravity (MHG) extraction of rosehips, as a novel application of solvent-free microwave extraction, previously conducted in a similar way only on mulberry, strawberry, and onion. The optimization was performed through a central composite design (CCD) by evaluating the effect of the experimental parameters on the yield; total polyphenol, flavonoid, and anthocyanin contents; radical scavenging activity; and content of vitamin C in the obtained extracts. As a result, the water moistening pretreatment was clearly revealed to possess a pivotal role in the quality of the rosehip extracts. Among the evaluated responses, the yield, the anthocyanin content, and the antioxidant activity were well described by the statistical model. Notably, the optimized MHG extract was compared with the ones obtained by conventional solvent extraction showing higher amounts of vitamin C, polyphenols, flavonoids, and anthocyanins, while the traditional extracts performed better in terms of yield. In conclusion, MHG represents a promising alternative to standard extraction methods for obtaining rosehip extracts rich in vitamin C and antioxidant compounds. In this respect, the results of our research support the employment of MHG on an industrial level for the production of rosehip-based food supplements enriched in vitamin C.

Cocoa and chocolate antioxidants might contribute to human health through, for instance, blood flow improvement or blood pressure and glycemia reduction, as well as cognitive function improvement. Unfortunately, polyphenol content is reduced during cocoa fermentation, drying, roasting and all the other phases involved in the chocolate production. Here, we investigated the evolution of the polyphenol content during all the different steps of chocolate production, with a special emphasis on roasting (3 different roasting cycles with 80, 100, and 130 °C as maximum temperature). Samples were followed throughout all processes by evaluating the total polyphenols content, the antioxidant power, the epicatechin content, and epicatechin mean degree of polymerization (phloroglucinol adducts method). Results showed a similar trend for total polyphenol content and antioxidant power with an unexpected bell-shaped curve: an increase followed by a decrease for the three different roasting temperatures. At the intermediate temperature (100 °C), the higher polyphenol content was found just after roasting. The epicatechin content had a trend similar to that of total polyphenol content but, interestingly, the mean degree of polymerization data had the opposite behavior with some deviation in the case of the highest temperature, probably due to epicatechin degradation. It seems likely that roasting can free epicatechin from oligomers, as a consequence of oligomers remodeling.

Recently, microwave-assisted hydrodistillation (MAH) has been reported as an innovative technique leading to increased essential oil (EO) extraction yield, coupled with reduced extraction time and energy costs. The EO of Carlina acaulis L. (Asteraceae), mainly constituted by carlina oxide (>95%) and conventionally obtained through traditional hydrodistillation (HD), has been reported as extremely effective against several arthropod vectors and pests of medical and economic importance with limited impact on non-target species, including mammals. This study aimed to the optimization of the EO extraction through MAH by using a one-step design of experiments (DoE) approach that allowed us to relate the characteristics of the produced EOs with the applied experimental conditions using mathematical models. The preliminary screening allowed us to optimize the protocol only by the extraction time, skipping complex data analysis. Moreover, the comparison of the optimized MAH conditions with traditional HD pointed out the higher efficiency of MAH in terms of EO yield (0.65 and 0.49% for MAH and HD, respectively) and extraction time (210 min for MAH). The results obtained confirmed the promising role that MAH could have in C. acaulis EO extraction, with increased yield and reduced extraction time, water consumption, and energy costs, and being employable on an industrial scale, with special reference to insecticidal and acaricidal formulations.

Background: Solvent-free microwave-assisted extraction (MAE) is a green extraction method capable of boosting the yield and quality profile of hemp essential oil when compared with other conventional extraction techniques. During this process, two by-products are produced, namely the aqueous residue containing bioactive phenolics and the residual deterpenated biomass, which can be used for further extraction and purification of phytocannabinoids. To date, the hemp industry has not utilized these products, although they can be valuable for the food, cosmetic, nutraceutical and pharmaceutical market., Results: This study assessed and optimized the variables affecting MAE efficiency, namely microwave irradiation power, extraction time and added water, which were studied using a central composite design approach, and results were used to optimize the extraction process for recovering three valuable fractions: essential oil, polyphenols and phytocannabinoids. The products obtained using the optimized conditions were characterized in terms of yield, chemical profile and antioxidant potential. Moreover, the by-products obtained during the optimized run were further analyzed in terms of their biological activity using both enzymatic and non-enzymatic assays. The aqueous residue demonstrated a powerful α-glucosidase inhibition, a good activity in terms of superoxide radical scavenging activity, a modest efficacy in terms of inhibition of advanced glycation end products formation and no activity in terms of lipase inhibition. The residual deterpenated biomass did not possess significant biological activity., Conclusion: This work demonstrated valorization of industrial hemp essential oil and its by-products, obtained by a sustainable and eco-friendly extraction method, through an almost waste-free approach. Cannabinoids as well as other valuable bioactive compounds such as glycosidic flavones may be recovered from the residues of the essential oil extraction, representing interesting substances in the pharmaceutical, cosmetic and nutraceutical fields. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Hand sanitizers represent a primary measure for the prevention of transmissible infections, whose use has been greatly increased during CoViD-19 pandemic. Most of the commercially available products are hydrogels, employing carbomers as thickening agents. However, few information is still available regarding performances of carbomers in hydroalcoholic media containing a percentage of alcohols ≥ 60% v/v as recommended for disinfection. The aim of this study was to investigate the colloidal behaviour of carbomer 974 and carbomer 980 in hydroalcoholic media containing from 50 to 80% w/w of alcohol (ethanol or isopropanol) and neutralised with triethanolamine or aminomethyl propanol. Both carbomers provide transparent hydrogels in water, but carbomer 980 should be preferred for the formulation of hydrogel with a percentage of alcohol ≥ 50% w/w for its better solvation. The critical alcohol concentration (CAlC), above which polymer precipitation occurs, depends on the type of alcohol and base used. Carbomer dispersions with a higher content of alcohol can be prepared using aminomethyl propanol rather than triethanolamine. The choice of the more suitable components is fundamental for the isopropanol-based dispersions since the CAlC is closer to the recommended concentrations for disinfection. Overall, these results provide helpful insights for the correct preparation of alcohol-based hand sanitizers using carbomers., (Copyright © 2022 Elsevier B.V. All rights reserved.)

High-resolution ultrasound spectroscopy (HR-US) is a spectroscopic technique using ultrasound waves at high frequencies to investigate the structural properties of dispersed materials. This technique is able to monitor the variation of ultrasound parameters (sound speed and attenuation) due to the interaction of ultrasound waves with samples as a function of temperature and concentration. Despite being employed for the characterization of several colloidal systems, there is a lack in the literature regarding the comparison between the potential of HR-US for the determination of phospholipid thermal transitions and that of other common techniques both for loaded or unloaded liposomes. Thermal transitions of liposomes composed of pure phospholipids (dimyristoylphosphatidylcholine, DMPC; dipalmitoylphosphatidylcholine, DPPC and distearoylphosphatidylcholine, DSPC), cholesterol and their mixtures were investigated by HR-US in comparison to the most commonly employed microcalorimetry (mDSC) and dynamic light scattering (DLS). Moreover, tramadol hydrochloride, caffeine or miconazole nitrate as model drugs were loaded in DPPC liposomes to study the effect of their incorporation on thermal properties of a phospholipid bilayer. HR-US provided the determination of phospholipid sol-gel transition temperatures from both attenuation and sound speed that are comparable to those calculated by mDSC and DLS techniques for all analysed liposomal dispersions, both loaded and unloaded. Therefore, HR-US is proposed here as an alternative technique to determine the transition temperature of phospholipid membrane in liposomes.

Cystic echinococcosis (CE) is one of the most important zoonotic diseases. The primary treatment is surgery and chemical sterilization of the parasitic layers by injection of a scolicidal agent. Available scolicidals possess side effects, and may cause postoperative complications. Several studies reported the scolicidal properties of monoterpene phenols and alcohols such as carvacrol, thymol, and geraniol. The present study aimed to develop, characterize, and assess monoterpene loaded microemulsions as novel green scolicidals products. For this purpose, microemulsions composing 0.37%, 0.75%, and 1.5% of monoterpenoid(s), thymol, carvacrol, and geraniol, alone or in binary or ternary mixtures were formulated. Samples were analyzed by visual inspection, polarizing optical microscope, and dynamic light scattering (DLS). The stability of the samples was evaluated up to a 3-month storage. For the scolicidal bioassay, samples at different concentrations of 200, 100, 50, 25, and 10 μg/ml were added to wells containing 10 4 viable protoscoleces and mortality rates were recorded at 2, 5, 10, and 20 min after exposure. Results of the present study showed that microemulsions formulated with 0.75% of pure carvacrol or the binary mixture of thymol and carvacrol at 0.375% are promising scolicidal agents., (© 2021 Wiley Periodicals LLC.)

New hydrophobic derivatives of cinnamic and hydroxycinnamic (ferulic and cumaric) acids obtained by chemical esterification of the carboxylic group with C10 linear alcohol were studied to evaluate their antioxidant capacity toward the superoxide anion and hydrogen peroxide in physiological buffer and in extra-virgin olive oil (EVO) or Nigella sativa oils. Results showed that cumaric and ferulic acids have higher antioxidants activity against superoxide anion and hydrogen peroxide than the other compounds. Cumaric acid and its C10-ester derivative were selected to be incorporated into EVO or Nigella sativa oil-based emulsions. The prepared emulsions had a comparable particle size distribution (in the range of 3-4 µm) and physical stability at least up to three months. Nigella sativa oil-based emulsions loaded with cumaric acid or its C10-ester showed a higher capacity to scavenger superoxide anion and hydrogen peroxide than EVO oil-based emulsions. In conclusion, cumaric acid or its C10-ester could promote the antioxidant properties of Nigella sativa oil when formulated as emulsions.

Black mulberry, Morus nigra L. (family: Moraceae), is a healthy food and medicinal plant. Microwave hydrodiffusion and gravity (MHG) is one of the most innovative applications of solvent-free microwave extraction. The aim of this study was to optimize for the first time the MHG solvent-free extraction of polyphenols and sugars from M. nigra fruits. Optimization was carried out using a central composite design (CCD) with selected responses such as extraction yield, total polyphenol (TPC), flavonoid (TFC), anthocyanin (TAC), and sugar (TSC) contents, in addition to DPPH radical scavenging, and α-glucosidase (AGHi), lipase (Li), and xanthine oxidase (XOi) inhibition as tools to evaluate the best parameters for efficient and rapid extraction of black mulberry. The optimized extract was characterized in terms of the aforementioned parameters to validate the models, and was further analyzed for 36 individual polyphenols using HPLC-MS/MS. The optimized MHG extract was finally compared with traditional extracts, and demonstrated much better performance in terms of TPC, TAC, and Li, while the traditional extracts showed better XOi and AGHi. In conclusion, MHG is a valuable green technique for the production of non-degraded black mulberry polyphenol-rich extract and we suggest its larger use in the pharmaceutical and food industries.

In this study, a comparison of the efficiency of the commercially available polydimethylsiloxane/divinylbenzene (PDMS/DVB) overcoated (OC) fiber used in direct immersion (DI) or in headspace (HS), has been performed by extracting volatiles through solid-phase microextraction (SPME) from a red wine and from a wine model to confirm the results. It was also investigated if a combination of DI followed by HS in a single assay (DI-HS) can provide improvements as compared to the use in DI or in HS only. Furthermore, the use of OC fiber in HS mode was compared with the use of the triphasic phase (TP, in PDMS/CAR/DVB), known to provide good results in this application. To have information also on fiber specificity, the detected analytes were subdivided into three classes depending on their boiling point. Results show that: OC fiber gives slightly better performance as compared to TP fiber, demonstrating a high efficiency of the OC fiber also in HS mode. Then, comparing the use of the commercial OC fiber in HS, DI and in the combined DI-HS mode, explored for the first time in this study to extract volatiles from wine, the combination DI-HS resulted to provide a more balanced efficiency for all the three groups of analytes, thus being a good compromise when the analytes have a broad range of volatility. Principal component analysis (PCA) and the design of experiment (DoE) were exploited to plan experiments and to help interpreting the results, highlighting that the combined DI-HS approach can be successfully applied to the characterization of wines and of other matrices, where analytes of interest have a wide range of volatility., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Quetiapine is an atypical antipsychotic approved for treating schizophrenia, bipolar depression, and mania but is frequently used in an off-label manner to control the behavioral and psychological symptoms of dementia in elderly patients with dementia. Due to the need to personalize doses for elderly patients with dementia, quetiapine tablet manipulation is widespread in hospital settings, long-term care facilities, and patient homes. The aim of this study was to assess the impact of the different splitting techniques on quetiapine fumarate tablets by analysing the obtained sub-divided tablets and to discuss compliance with the European Pharmacopoeia limits on whole and split tablets. Quetiapine fumarate tablets of two dose strengths were taken at random (in a number able to assure a power of 0.8 during statistical comparison) and were split with a kitchen knife or tablet cutter. The weight and the drug content were determined for each half tablet. The obtained data were compared to the European Pharmacopoeia limits. The differences between the different splitting techniques were statistically tested. Data showed that split tablets, independently of the dose strength and the technique employed, were not compliant with the European Pharmacopoeia specifications for both entire and subdivided tablets in terms of weight and content uniformity. Thus, such a common practice could have potential effects on treatment efficacy and toxicity, especially when also considering the fragility of the elderly target population in which polypharmacotherapy is very common. These results indicate a compelling need for flexible quetiapine formulations that can assure more accurate dose personalization.

Ajowan ( Trachyspermum ammi L.) is a spice traditionally used in Middle Eastern medicine and contains a valuable essential oil (EO) exploited in different fields, such as pharmaceutics, agrochemicals and food additives. This EO is mostly characterized by the thymol to which most of its biological properties are related. Given the economic value of ajowan and its increasing demand across the globe, the extraction method used for its EO is of paramount importance in terms of quality and quantity of the final product. In the present study, we used the design of experiment (DoE) approach to study and optimize the extraction of the ajowan EO using the microwave-assisted extraction (MAE), a novel extraction technique with high efficiency, low energy consumption, short process length and low environmental impact. A two-step DoE (screening followed by surface response methodology) was used to reduce the number of experiments and to improve the cost/benefit ratio. Reliable mathematical models, relating the more relevant EO features with the extraction conditions, were obtained and used to identify the best experimental conditions able to maximize the yield and thymol concentration. The optimized MAE procedure assures an EO with a higher yield and thymol amount compared with the standard hydrodistillation procedure.

Cellulosic-based thickeners are commonly used in the preparation of hydro-alcoholic hand sanitisers. Yet, little is known about the behaviour of these polymeric dispersions in hydro-alcoholic mixtures. Here, we studied the dispersion ability and rheology of hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose and sodium carboxymethyl cellulose in water-ethanol mixtures. Hydroxypropyl cellulose formed transparent dispersions across the entire range of ethanol concentrations, while a critical ethanol concentration (CEC), above which dispersions became turbid, was found for all the other polymers. At and below the CEC, all the rheological parameters followed a bell-like shape profile as a function of ethanol concentration. Moreover, the molecular weight and degree of substitution of the polymers influenced the rheological properties. The CEC and rheological behaviour of the dispersions were both dependent on the ethanol/polymer and water/polymer interactions. As hand disinfectants should contain 60-95% ethanol, polymers of higher CEC, such as hydroxypropyl cellulose and hydroxypropyl methylcellulose, are recommended., (Copyright © 2021 Elsevier B.V. All rights reserved.)

During the last decade, an innovative lab on a chip technology known as microfluidics became popular in the pharmaceutical field to produce nanomedicines in a scalable way. Nevertheless, the predominant barriers for new microfluidics users are access to expensive equipment and device fabrication expertise. 3D printing technology promises to be an enabling new field that helps to overcome these drawbacks expanding the realm of microfluidics. Among 3D printing techniques, fused deposition modeling allows the production of devices with relatively inexpensive materials and printers. In this work, we developed two different microfluidic chips designed to obtain a passive micromixing by a "zigzag" bas-relief and by the presence of "split and recombine" channels. Computational fluid dynamics studies improved the evaluation of the mixing potential. A fused deposition modeling 3D printer was used to print the developed devices with polypropylene as manufacturing material. Then, two different model nanocarriers (i.e., polymeric nanoparticles and liposomes), loading cannabidiol as model drug, were formulated evaluating the influence of manufacturing parameters on the final nanocarrier characteristics with a design of experiments approach (2-level full factorial design). Both the chips showed an effective production of nanocarriers with tunable characteristics and with an efficient drug loading. These polypropylene-based microfluidic chips could represent an affordable and low-cost alternative to common microfluidic devices for the effective manufacturing of nanomedicines (both polymer- and lipid-based) after appropriate tuning of manufacturing parameters., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Disintegration is the de-aggregation of particles within tablets upon exposure to aqueous fluids. Being an essential step in the bioavailability cascade, disintegration is a fundamental quality attribute of immediate release tablets. Although the disintegration phenomenon has been studied for over six decades, some gaps of knowledge and research questions still exist. Three reviews, published in 2015, 2016 and 2017, have discussed the literature relative to tablet disintegration and summarised the understanding of this topic. Yet, since then more studies have been published, adding to the established body of knowledge. This article guides a step forward towards the comprehension of disintegration by reviewing, concisely, the most recent scientific updates on this topic. Initially, we revisit the mechanisms of disintegration with relation to the three most used superdisintegrants, namely sodium starch glycolate, croscarmellose sodium and crospovidone. Then, the influence of formulation, storage, manufacturing and media conditions on disintegration is analysed. This is followed by an excursus on novel disintegrants. Finally, we highlight unanswered research questions and envision future research venues in the field., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Most insecticides commonly used in storage facilities are synthetic, an issue that generates concerns about food safety and public health. Therefore, the development of eco-friendly pest management tools is urgently needed. In the present study, a 6% ( w/w ) Hazomalania voyronii essential oil-based nanoemulsion (HvNE) was developed and evaluated for managing Tribolium confusum , T. castaneum , and Tenebrio molitor , as an eco-friendly wheat protectant. Larval and adult mortality was evaluated after 4, 8, and 16 h, and 1, 2, 3, 4, 5, 6, and 7 days, testing two HvNE concentrations (500 ppm and 1000 ppm). T. confusum and T. castaneum adults and T. molitor larvae were tolerant to both concentrations of the HvNE, reaching 13.0%, 18.7%, and 10.3% mortality, respectively, at 1000 ppm after 7 days of exposure. However, testing HvNE at 1000 ppm, the mortality of T. confusum and T. castaneum larvae and T. molitor adults 7 days post-exposure reached 92.1%, 97.4%, and 100.0%, respectively. Overall, the HvNE can be considered as an effective adulticide or larvicide, depending on the target species. Our results highlight the potential of H . voyronii essential oil for developing green nanoinsecticides to be used in real-world conditions against key stored-product pests.

Flavours and fragrances are volatile compounds of large interest for different applications. Due to their high tendency of evaporation and, in most cases, poor chemical stability, these compounds need to be encapsulated for handling and industrial processing. Encapsulation, indeed, resulted in being effective at overcoming the main concerns related to volatile compound manipulation, and several industrial products contain flavours and fragrances in an encapsulated form for the final usage of customers. Although several organic or inorganic materials have been investigated for the production of coated micro- or nanosystems intended for the encapsulation of fragrances and flavours, polymeric coating, leading to the formation of micro- or nanocapsules with a core-shell architecture, as well as a molecular inclusion complexation with cyclodextrins, are still the most used. The present review aims to summarise the recent literature about the encapsulation of fragrances and flavours into polymeric micro- or nanocapsules or inclusion complexes with cyclodextrins, with a focus on methods for micro/nanoencapsulation and applications in the different technological fields, including the textile, cosmetic, food and paper industries.

Platelet-rich plasma (PRP) is a nontransfusional hemocomponent, considered as a powerful concentrate of growth factors (GFs) therapeutically used to stimulate tissue regeneration. The use of autologous PRP, as the patient's own biological material, for therapeutic purposes represents a safe and effective alternative to conventional treatments in both human and veterinary medicine. The aim of this study was the characterization of canine PRP from rheological and biological points of view. Thus, a characterization of the viscoelastic properties of the PRP systems was performed in order to clarify the influence of different calcium concentrations, in the presence of autologous thrombin-rich solution, on the PRP gels' mechanical properties, from which the applicability of these systems in biomedical treatments is strongly dependent. Then, an evaluation of the content of GFs in PRP, activated or not with thrombin, and stored at different temperatures (37 °C and -20 °C) was performed over time, outlining, for the first time, the importance of the effect of physiological temperature (37 °C) on the production of GFs. A clinical case study conducted in a dog with a complete rupture of the common calcaneal tendon (Achilles tendon) confirmed the relevance of this hemocomponent in the daily veterinary clinical activity and the potential translational value for human health.

Disintegration is the first event in the bioavailability cascade after the ingestion of immediate release tablets. Although the influence of various physico-chemical parameters of media on tablet disintegration has been investigated in depth, the role of temperature has received much less attention. Probing the effect of temperature on disintegration is important in order to understand if previous in vitro studies conducted at room temperature can be related to those performed at body temperature. Moreover, from a biorelevant point of view, a tablet could be co-ingested with a cold or hot drink, inducing transient variations of intragastric temperature; state of fever could also elevate body temperature. Here, we studied the effect of temperature on disintegration of directly compressed tablets made of disintegrants alone and in combination with commonly used diluents and binders, using an image analysis technique as well as a compendial disintegration apparatus. Our results indicate that temperature in the range of 23°C to 41°C had a positive effect on disintegration: tablets tested at higher temperatures exhibited up to 2.9-fold faster disintegration than those tested at lower temperatures. The extent of temperature effect on disintegration time was significantly influenced by the composition of the formulations. Overall, the findings of this study suggest that disintegration results obtained in vitro at room temperature can be qualitatively, but not quantitatively, compared to those obtained at body temperature. We also speculate that although temperature had a moderate influence on in vitro disintegration, the magnitude of this effect is unlikely to impact the oral bioavailability in vivo., (Copyright © 2020 Elsevier B.V. All rights reserved.)