Mechanical characterization of pharmaceutical solids: a comparison between rheological tests performed under static and dynamic porosity conditions.

The aim of this work was to verify how and to what extent rheological tests, carried out under dynamic (Heckel) and static (creep, stress/strain) porosity conditions, may serve as a valuable complement to the classic Heckel tests in the characterization of viscoelastic and densification properties of solid materials for pharmaceutical use. Six different modified (pregelatinized) starches were compressed in a rotary tablet machine equipped to measure force and punch displacement. Tablets were obtained using flat-faced 6 mm diameter punches at different compression pressures. Compression cycles performed at the maximal pressure of 200 MPa were used to build the Heckel plots. Ejected tablets at the 10%, 20%, 30%, and 40% porosity levels were used for the stress/strain and creep tests. Parameters obtained with both types of tests were consistent with each other. In particular, among the six starches, lower viscosity values corresponded to lower PY values, and lower elastic modulus values corresponded to lower elastic recovery of the tablet. Mechanical properties of materials can be better characterized if viscoelastic tests performed under dynamic porosity conditions (Heckel analysis) are supported by classical viscoelastic tests carried out under conditions of static porosity

Engineered Carrier with a Long Time of Flight (TOF) to Improve Drug Delivery From Dry Powder Inhalation Aerosols

A lactose carrier with long TOF was engineered to improve drug deposition from DPIs. The particles were engineered by contacting spray-dried particles with a solvent in which these have a poor solubility. The process increased the particles hollow volume without affecting their original shape. The long TOF was demonstrated by carrier deposition in the lower stage of the TSI, which was up to 9 -fold higher compared to the conventional lactose. The highest deposition of the long TOF carrier was obtained at the lowest inhalation flow rate (24 L/min). The % Fine Particle Fraction of salbutamol sulphate was up to 50% when long TOF carrier was used. Importantly, this study has shown that adhesion drug/carrier has no negative effect on drug deposition, when a long TOF carrier is used

High-Resolution Ultrasound Spectroscopy for the Determination of Phospholipid Transitions in Liposomal Dispersions

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

Tablet splitting in elderly patients with dementia: The case of quetiapine

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

An overview of natural polymers as reinforcing agents for 3D printing

Three-dimensional (3D) printing, or additive manufacturing, is a group of innovative technologies that are increasingly employed for the production of 3D objects in different fields, including pharmaceutics, engineering, agri-food and medicines. The most processed materials by 3D printing techniques (e.g., fused deposition modelling, FDM; selective laser sintering, SLS; stereolithography, SLA) are polymeric materials since they offer chemical resistance, are low cost and have easy processability. However, one main drawback of using these materials alone (e.g., polylactic acid, PLA) in the manufacturing process is related to the poor mechanical and tensile properties of the final product. To overcome these limitations, fillers can be added to the polymeric matrix during the manufacturing to act as reinforcing agents. These include inorganic or organic materials such as glass, carbon fibers, silicon, ceramic or metals. One emerging approach is the employment of natural polymers (polysaccharides and proteins) as reinforcing agents, which are extracted from plants or obtained from biomasses or agricultural/industrial wastes. The advantages of using these natural materials as fillers for 3D printing are related to their availability together with the possibility of producing printed specimens with a smaller environmental impact and higher biodegradability. Therefore, they represent a “green option” for 3D printing processing, and many studies have been published in the last year to evaluate their ability to improve the mechanical properties of 3D printed objects. The present review provides an overview of the recent literature regarding natural polymers as reinforcing agents for 3D printing

Hyperlipidemia control using the innovative association of lupin proteins and chitosan and α-cyclodextrin dietary fibers: food supplement formulation, molecular docking study, and in vivo evaluation

A dietary supplement potentially employed for the treatment and/or prevention of hyperlipidemia was developed. The proposed product is composed of a combination of natural macromolecules as chitosan (CH), α-cyclodextrin (α-CD), and lupin proteins (LP). First, the anti-hyperlipidemic effect of the α-CD and LP binary mixture was assessed and compared to that of the extensively utilized anti-hyperlipidemic CH, using a hyperlipidemic rat model. The anti-hyperlipidemic effect of their combination was also demonstrated. Additionally, ligand–target and protein–protein docking studies were performed. The in vivo results displayed that on intergroup comparison, blending CH, α-CD, and LP promised a superior therapeutic effect over α-CD and LP mixture, CH, and the marketed atorvastatin, potentiating a considerable reduction of serum lipid profile and the calculated atherogenic risk predictor indices. Molecular docking study revealed a weak hydrophobic cholesterol–CH and cholesterol–α-CD interactions, while protein–protein docking study showed a good lipase–LP interaction, involving eight hydrogen bonds. Then, on the base of the in vivo and docking study results, a tablet formulation was produced aimed to overcome the negative technological effects of the anti-hyperlipidemic macromolecules: long disintegration time and tablets mechanical resistance. The optimized tablet formulation has a disintegration time shorter than 15 min and a weight loss from friability test lower than 1%, which are in line with the regulatory specifications for uncoated tablets. Overall, this anti-hyperlipidemic formulation is attractive for the dietary and nutraceutical market, despite further clinical studies are required to assess the efficacy, possible side effects, and product compliance

Effect of Cocoa Roasting on Chocolate Polyphenols Evolution

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

A comprehensive comparative study among the newly developed Pure Brew method and classical ones for filter coffee production

Pure Brew represents a real innovation because it allows one to obtain a fast-filter coffee with an espresso machine without the need for the barista to purchase additional equipment. This study investigated the difference between Pure Brew, French Press, V60 and AeroPress in terms of physical and chemical characteristics, extraction yields, volatile compounds by GC-MS and bioactive molecules by UHPLC-MS of resulting coffee, studying also powder particle size. Finally, main results showed that Pure Brew is comparable to other methods available on the market, but also showed the highest levels of caffeine (598.28 ± 8.84 and 556.13 ± 1.22 μg/mL) and total bioactive compounds (1726.8 ± 22.4 and 1407.89 ± 9.53 μg/mL) in medium and dark roasted coffee, compared to the other brewing methods. Pure Brew also displayed the most positive results in extraction yields, it falls into the ideal extraction percentage (18–22%) at the three different degrees of roasting, versus the other brewing methods. At the light roast, for Pure Brew were discovered the most olfactometrically impactful molecules of the study at GC-MS, 5-Methyl 2-furancarboxaldehyde, Furfural, and 2-Furanmethanol, connected with positive remarks, associated with almond and sweet

Optimization of Solvent-Free Microwave-Assisted Hydrodiffusion and Gravity Extraction of Morus nigra L. Fruits Maximizing Polyphenols, Sugar Content, and Biological Activities Using Central Composite Design

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 a-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

Sustainability of Urban Growth Forms in Metropolitan Area of Buenos Aires

Esta ponencia expone avances de una investigación cuyo objetivo es identificar indicadores de sustentabilidad urbana que contribuyan a evaluar el desempeño de distintas formas de crecimiento urbano y orientar la conformación de futuros observatorios que permitan monitorear el desempeño ambiental de unidades territoriales de análisis (UTA) dentro del AMBA. La metodología aplicada, basada en distintos autores que analizan la evolución del crecimiento urbano fue adaptada al contexto local y a los casos de estudio. Se seleccionaron cuatro unidades de análisis con diferente forma de crecimiento en dos municipios del AMBA. Se definieron variables para desarrollar indicadores, integrando sistemas de evaluación de sustentabilidad urbana y ambiental. Se relevaron las UTAs seleccionadas y realizaron ensayos bioclimáticos y mediciones in situ. Los resultados, permiten sacar las conclusiones comparativas iniciales del desempeño bioambiental de las unidades a fin de evaluar aspectos de sustentabilidad, tanto a escala de la unidad, como en relación al contexto urbano.This paper presents advances of a research that is aimed to identify urban sustainability indicators which help to evaluate the performance of various forms of city growth and guide the establishment of observatories for monitoring environmental performance of territorial units of analysis, transferable to different AMBA sectors. The methodology applied, based in different theories that interpret changes of urbanization in the cities, was adapted to local context. Four units of analysis of different growth form were selected in two municipalities in the AMBA. From the integration of different evaluation systems for urban sustainability, variables were defined to develop indicators. The selected units were analized and were made in situ environmental measurements. The results allows to obtain initial comparative conclusions about bioambiental performance of the units, aimed to evaluate some sustainability aspects both at the unit as in relation to urban context.Eje: Sustentabilidad urbana (Actas).Facultad de Arquitectura y Urbanism