Predicting the Stability of Lyophilized Human Serum Albumin Formulations Containing Sucrose and Trehalose Using Solid-State NMR Spectroscopy: Effect of Storage Temperature on 1H T1 Relaxation Times.

In a lyophilized protein/disaccharide system, the ability of the disaccharide to form a homogeneous mixture with the protein and to slow the protein mobility dictates the stabilization potential of the formulation. Human serum albumin was lyophilized with sucrose or trehalose in histidine, phosphate, or citrate buffer. 1H T1 relaxation times were measured by solid-state NMR spectroscopy and were used to assess the homogeneity and mobility of the samples after zero, six, and twelve months at different temperatures. The mobility of the samples decreased after 6 and 12 months storage at elevated temperatures, consistent with structural relaxation of the amorphous disaccharide matrix. Formulations with sucrose had lower mobility and greater stability than formulations with trehalose.

Exploring conventional and emerging dehydration technologies for slurry/liquid food matrices and their impact on porosity of powders: A comprehensive review.

The contribution of dehydration to the growing market of food powders from slurry/liquid matrices is inevitable. To overcome the challenges posed by conventional drying technologies, several innovative approaches have emerged. However, industrial implementation is limited due to insufficient information on the best-suited drying technologies for targeted products. Therefore, this review aimed to compare various conventional and emerging dehydration technologies (such as active freeze, supercritical, agitated thin-film, and vortex chamber drying) based on their fundamental principles, potential applications, and limitations. Additionally, this article reviewed the effects of drying technologies on porosity, which greatly influence the solubility, rehydration, and stability of powder. The comparison between different drying technologies enables informed decision-making in selecting the appropriate one. It was found that active freeze drying is effective in producing free-flowing powders, unlike conventional freeze drying. Vortex chamber drying could be considered a viable alternative to spray drying, requiring a compact chamber than the large tower needed for spray drying. Freeze-dried, spray freeze-dried, and foam mat-dried powders exhibit higher porosity than spray-dried ones, whereas supercritical drying produces nano-porous interconnected powders. Notably, several factors like glass transition temperature, drying technologies, particle aggregation, agglomeration, and sintering impact powder porosity. However, some binders, such as maltodextrin, sucrose, and lactose, could be applied in controlled agglomeration to enhance powder porosity. Further investigation on the effect of emerging technologies on powder properties and their commercial feasibility is required to discover their potential in liquid drying. Moreover, utilizing clean-label drying ingredients like dietary fibers, derived from agricultural waste, presents promising opportunities.

Viscoelastic properties of decellularized and freeze-dried human dermis between i909c and 40cC.

BACKGROUND: Human donor skin is processed to make the acellular dermis matrix (ADM) for tissue repair and regeneration. There is no data on the viscoelastic properties of ADM at room and subzero temperatures. OBJECTIVE: The work evaluated the temperature dependence of viscoelastic properties of freeze-dried ADM. MATERIALS AND METHODS: Donor skin was de-epidermized, de-cellularized and freeze-dried with trehalose as the lyo-protectant. Glass transition of freeze-dried ADM was measured by differential scanning calorimeter (DSC), and viscoelastic properties were examined by dynamic mechanical analyzer (DMA). RESULTS: At the low moisture range (1.4 +/- 0.5%), the glass transition temperature (Tg) of freeze-dried ADM was 90 degree C to 100 degree C. As the moisture content increased, the Tg decreased steadily. At the high moisture range (10.8 +/- 2.9%), the Tg was 40 degree C to 60 degree C. There were large donor-to-donor variations in viscoelastic properties of freeze-dried ADM as demonstrated by the changes in storage modulus (G'), loss modulus (G") and damping factor tan delta (G"/G'). However, the trends of the temperature dependence for G', G" and tan delta were similar among all 8 donors. For each donor, changes in G' and G" were relatively small between -90 degree C and 40 degree C, and G' was at least one order of magnitude greater than G". Two viscoelastic relaxations were observed in freeze-dried ADM, one at -20 degree C and the other at -60 degree C respectively. CONCLUSION: Freeze-dried ADM was protected in the glassy carbohydrate matrix. DMA observed two viscoelastic relaxations (i.e., alpha process at -20 degree C and beta process at -60 degree C). Overall changes in G' and G'' of freeze-dried ADM were relatively small within one order of magnitude between -90 degree C and 40 degree C. https://doi.org/10.54680/fr24110110612.

Effect of Annealing on Visible-Bubble Formation and Stability Profiles of Freeze-Dried High Concentration Omalizumab Formulations.

In the clinical application of freeze-dried highly concentrated omalizumab formulations, extensive visible bubbles (VBs) can be generated and remain for a long period of time in the reconstitution process, which greatly reduces the clinical use efficiency. It is necessary to understand the forming and breaking mechanism of VBs in the reconstitution process, which is a key factor for efficient and safe administration of biopharmaceutical injection. The effects of different thermal treatments on the volume of VBs and stability of omalizumab, mAb-1, and mAb-2 were investigated. The internal microvoids of the cake were characterized by scanning electron microscopy and mercury intrusion porosimetry. Electron paramagnetic resonance was applied to obtain the molecular mobility of the protein during annealing. A large number of VBs were generated in the reconstitution process of unannealed omalizumab and remained for a long period of time. When annealing steps were added, the volume of VBs was dramatically reduced. When annealed at an aggressive temperature (i.e., -6 °C), although the volume of VBs decreased, the aggregation and acidic species increased significantly. Thus, our observations highlight the importance of setting an additional annealing step with a suitable temperature, which contributes to reducing the VBs while maintaining the stability of the high concentration freeze-dried protein formulation.

Strong double networked hybrid cellulosic foam for passive cooling.

Up to now, energy conservation, emission reduction, and environmental protection are still the goals that humanity continuously pursues. Passive radiative cooling is a zero-consumption cooling technology, which gains more and more attention. However, the contraction between mechanical strength and cooling performance of traditional radiative cooling materials still limits their scalable production. In this work, we developed a strong double-networked hybrid cellulosic foam via crosslinking recyclable CNF and PVA with a silane coupling agent in the freeze-drying process. Meanwhile, nano zinc oxide and MOF were added to improve the mechanical and solar scattering of foam. Benefiting from the synergistic solar scattering of ZnO and MOF and the stable double crosslinking network, the as-prepared hybrid cellulosic foam exhibits high solar reflectivity of 0.965, high IR emissivity of 0.94, ultrahigh mechanical strength of and low thermal conductivity. Based on above results, the hybrid cellulosic foam shows high-performance daytime cooling efficiency of 7.5 °C under direct sunlight in the hot region (Nanjing, China), which can serve as outdoor thermal-regulation materials. This work demonstrates that biomass materials possess the enormous potential of in thermal regulating materials, and also provides great possibilities for their applications in energy conservation, environmental protection and green building materials.

How spray drying processing and solution composition can affect the mAbs stability in reconstituted solutions for subcutaneous injections. Part II: Exploring each protein stabilizer effect.

Despite extensive research in spray drying of biopharmaceuticals, identifying the optimal formulation composition and process conditions to minimize the various stresses a biopharmaceutical undergoes during this drying process. The current study extends previous research on investigating how spray drying processing and solution composition can affect the stability of monoclonal antibodies (mAbs) in reconstituted solutions for subcutaneous injections. The decoupling process stresses on a model mAb (mAb-A) compared to the effect of coupled spray-drying stresses revealed that excipients and protein concentration had a more pronounced effect on stabilizing mAb-A against shear and thermal/dehydration stresses than spray drying operating conditions. These results prompted the continuation of the study, with the aim to investigate in greater depth the effect of mAb-A concentration in the formulation designated to spray-drying and then the effect of type and the concentration of individual excipients (sugars, amino acids and surfactants). The outcomes of this investigation suggest that a general increase in the concentration of excipients, particularly surfactants, correlates with a reduction in aggregation and turbidity observed in the reconstituted spray-dried mAb-A powders. These results, contribute to the identification of a suitable composition for a spray-dried mAb-A powder that ensures robust stability of the protein in reconstituted solutions intended for subcutaneous injection. This valuable insight has important implications for advancing the development of pharmaceutical formulations with enhanced stability and efficacy.

How spray drying processing and solution composition can affect the mAbs stability in reconstituted solutions for subcutaneous injections. Part I: Contribution of processing stresses against composition.

Spray drying is increasingly being applied to process biopharmaceuticals, particularly monoclonal antibodies (mAbs). However, due to their protein nature, mAbs are susceptible to degradation when subjected to various stresses during a drying process. Despite extensive research in this domain, identifying the appropriate formulation composition and spray drying conditions remains a complex challenge, requiring further studies to enhance the understanding on how process and formulation parameters impact mAb stability in reconstituted solutions. This research aims to explore spray drying as technique for producing pharmaceutical mAbs-based powders intended for reconstitution and subcutaneous injection. In the initial phase of this study, using a model mAb (mAb-A), the influence of dissociated and coupled process stresses on protein stability after solution reconstitution was investigated. The findings revealed a detrimental interplay of mechanical, interfacial, and thermal/dehydration stresses on mAb-A stability, notably characterized by an increase in protein aggregation. Subsequently, in a second phase, the study delved into the impact of spray drying processing conditions, the level of excipients, and protein concentration on mAb-A aggregation in reconstituted solutions. The obtained results highlighted the critical role of formulation composition as a parameter deserving further study, specifically concerning the selection of type and concentration of stabilizers to be added in the liquid mAb-A solution to be dried.

Freezing-mediated formation of supraproteins using depletion forces.

Hypothesis Long-acting formulations such as microparticles, injectable depots and implantable devices can realize spatiotemporally controlled delivery of protein drugs to extend their therapeutic in vivo half-lives. To efficiently encapsulate the protein drugs into such drug delivery systems, (sub)micron-sized protein particles are needed. The formation of micronized supraproteins can be induced through the synergistic combination of attractive depletion forces and freezing. The size of the supraproteins can be fine-tuned from submicron to several microns by adjusting the ice crystallization rate through the freeze-quench depth, which is set by the target temperature. Methods Supraprotein micron structures were prepared from protein solutions under various conditions in the presence and absence of nonadsorbing polyethylene glycol. Scanning electron microscopy and dynamic light scattering were employed to determine the sizes of the supraproteins and real-time total internal reflection fluorescent microscopy was used to follow the supraprotein formation during freezing. The protein secondary structure was measured before and after micronization by circular dichroism. A phase diagram of a protein-polyethylene glycol mixture was theoretically predicted to investigate whether the depletion interaction can elucidate the phase behavior. Findings Micronized protein supraparticles could be prepared in a controlled manner by rapid freeze-drying of aqueous mixtures of bovine serum albumin, horseradish peroxidase and lysozyme mixed with polyethylene glycol. Upon freezing, the temperature quench initiates a phase separation process which is reminiscent of spinodal decomposition. This demixing is subsequently arrested during droplet phase separation to form protein-rich microstructures. The final size of the generated protein microparticles is determined by a competition between phase separation and cooling rate, which can be controlled by target temperature. The experimental phase diagram of the aqueous protein-polyethylene glycol dispersion aligns with predictions from depletion theory for charged colloids and nonadsorbing polymers.

Innovative vs classical methods for drying heterotrophic Chlorella vulgaris: Impact on protein quality and sensory properties.

Drying is a necessary step in the microalgae production chain to reduce microbial load and oxidative degradation of the end product. Depending on the differences in applied temperature and treatment time, the process of drying can have a substantial impact on protein quality and aroma, important characteristics determining the incorporation potential in food products. In this study, we compared the drying of heterotrophic Chorella vulgaris with both innovative (agitated thin film drying (ATFD), pulse combustion drying (PCD) and solar drying (SolD)) and commonly used drying techniques (spray drying (SprD) and freeze drying (FD)). To evaluate the impact on protein quality, we evaluated techno-functional properties, in vitro digestibility (INFOGEST) as well as protein denaturation using differential scanning calorimetry (DSC). A sensory analysis was performed by a trained expert panel, combined with headspace solid-phase microextraction (HS-SPME) - gas chromatography-mass spectrometry (GC-MS) to determine volatile organic compounds (VOCs). ATFD was found to increase techno-functional properties such as gelling, water holding and solubility as well as in vitro protein digestibility. These observations could be related to induced cell disruption and protein denaturation by ATFD. Sensory analysis indicated an increased earthy off-flavor after ATFD. Interestingly, the high-temperature PCD led to an increase in cacao odor while low-temperature FD resulted in lower flavor, odors and VOCs. These results demonstrate that protein quality and sensorial properties of C. vulgaris can be steered through the type of drying, which could help in the selection of application-specific drying methods. Overall, this work could promote the incorporation of microalgal single cell proteins in different innovative food products.

Lyophilization for bacteria preservation: a promising approach for Yersinia pestis strains from an unique collection in Brazil (Fiocruz-CYP).

Yersinia pestis, the causative agent of plague, is a highly virulent bacterium that poses a significant threat to human health. Preserving this bacterium in a viable state is crucial for research and diagnostic purposes. This paper presents and evaluates a simple lyophilization protocol for the long-term storage of Y. pestis strains from Fiocruz-CYP, aiming to explore its impact on viability and long-term stability, while replacing the currently used methodologies. The lyophilization tests were conducted using the non-virulent Y. pestis strain EV76, subjected to the lyophilization process under vacuum conditions. Viability assessment was performed to evaluate the effects of lyophilization and storage conditions on Y. pestis under multiple temperature conditions (- 80 °C, - 20 °C, 4-8 °C and room temperature). The lyophilization protocol employed in this study consistently demonstrated its efficacy in maintaining high viability rates for Y. pestis samples in a up to one year follow-up. The storage temperature that consistently exhibited the highest recovery rates was - 80 °C, followed by - 20 °C and 4-8 °C. Microscopic analysis of the post-lyophilized cultures revealed preserved morphological features, consistent with viable bacteria. The high viability rates observed in the preserved samples indicate the successful preservation of Y. pestis using this protocol. Overall, the presented lyophilization protocol provides a valuable tool for the long-term storage of Y. pestis, offering stability, viability, and functionality. By refining the currently used methods of lyophilization, this protocol can improve long-term preservation for Y. pestis strains collections, facilitating research efforts, diagnostic procedures, and the development of preventive and therapeutic strategies against plague.

Sensory properties of rehydrated Toona sinensis shoots after dehydrated by different drying methods and association with gamma-glutamyl transferase reaction.

Sulfur-containing compounds are responsible for the aroma of Toona sinensis shoot (TS). In this study, vacuum-freeze-drying (VFD), microwave-drying (MD), and hot-air-drying at 100 and 40 °C (HAD100 and HAD40, respectively), were applied to dehydrate perishable TS for preservation. VFD-TS retained most aroma of fresh/raw TS after rehydration. The content of sulfur-containing compounds reached to 118.00 µg/g with leading by methyl thiirane, (E,E)/(E,Z)/(Z,Z)-bis-(1-propenyl) disulfides, and (Z)/(E)-2-mercapto-3,4-dimethyl-2,3-dihydrothiophenes accounting for 86.33 %. They were undetected in the rehydrated MD-TS and HAD100-TS, as the indigenous enzymes in TS were deactivated under their dehydration conditions. Interestingly, the sulfur-containing compounds was restored by 77.47 % after the TS was treated by gamma-glutamyl transferase (GGT). Thus, the release of sulfur-containing compounds from TS could depend on GGT reaction. It was different from alliaceous vegetables relying on alliinase reaction. The results revealed the aroma formation in TS and provided an approach to enhance the aroma of TS dried by different methods.

Hot-air drying vs. lyophilization of sugar beet flakes for efficient pectin recovery and influence of extraction conditions on pectin physicochemical properties.

This study assessed the influence of drying pretreatment and extraction conditions (type of acid and particle size of plant material) on the yield and physicochemical properties of pectin from sugar beet flakes resulted as by-product of sugar beet processing in the sugar industry. The results indicated that the drying conditions (hot-air drying and lyophilization) affected the extraction yield, the chemical composition of pectin, its color, degree of methylation and acetylation, molecular weight, and its rheological and emulsifying properties. The best results for pectin yield (16.20%), galacturonic acid content (91.19 g/100 g), degree of methylation and acetylation (66.93 and 23.87%), and molecular weight (3.89 × 105 g/mol) were obtained when sugar beet flakes were pretreated by hot-air drying, and the extraction was made with citric acid using plant material with particle sizes of 125-200 µm. This pectin also had high emulsion activity (51.42%) and emulsion stability (88.03%). The FT-IR spectra were similar, while pectin thermal behavior was affected by the drying pretreatment and extraction conditions. The results of this study showed that from this by-product of the sugar industry it can be extracted high quality pectin with rheological and emulsifying properties that are superior to commercial citrus and apple pectin.

Combinations of arginine and pullulan reveal the selective effect of stabilization mechanisms on different lyophilized proteins.

The stability of lactate dehydrogenase (LDH) and ß-galactosidase (ß-gal), incorporated in arginine/pullulan (A/P) mixtures at various weight ratios by lyophilization, was determined. The physicochemical characteristics of various A/P mixtures were assessed. With decreasing A/P ratios, the glass transition temperature of the formulations increased. Furthermore, arginine crystallization due to high relative humidity (RH) exposure was prevented at an A/P weight ratio of 4/6 or less. When stored at 0 % RH / 60 °C for 4 weeks, arginine was superior to pullulan as stabilizer. During storage at 43 % RH / 30 ℃ for 4 weeks, the enzymatic activity of LDH was best retained at an A/P weight ratio of 2/8, while ß-gal activity was relatively well-retained at A/P weight ratios of both 8/2 and 2/8. LDH seemed to be more prone to degradation in the rubbery state. In the glassy state, ß-gal degraded faster than LDH. Solid-state nuclear magnetic resonance spectroscopy showed that (labeled) arginine experienced a different interaction in the two protein samples, reflecting a modulation of long-range correlations of the arginine side chain nitrogen atoms (Nε, Nη). In summary, LDH stabilization in the A/P matrix requires vitrification. Further stabilization difference between LDH and ß-gal may be dependent on the interaction with arginine.

Intranasal delivery of thin-film freeze-dried monoclonal antibodies using a powder nasal spray system.

Monoclonal antibodies (mAbs) administered intranasally as dry powders can be potentially applied for the treatment or pre-exposure prevention of viral infections in the upper respiratory tract. However, a method to transform the mAbs from liquid to dry powders suitable for intranasal administration and a device that can spray the dry powders to the desired region of the nasal cavity are needed to fully realize the potentials of the mAbs. Herein, we report that thin-film freeze-dried mAb powders can be sprayed into the posterior nasal cavity using Aptar Pharma's Unidose (UDS) Powder Nasal Spray System. AUG-3387, a human-derived mAb that neutralizes the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was used in the present study. First, we prepared thin-film freeze-dried AUG-3387 powders (i.e., TFF AUG-3387 powders) from liquid formulations containing different levels of mAbs. The TFF AUG-3387 powder with the highest solid content (i.e., TFF AUG-3387C) was then chosen for further characterization, including the evaluation of the plume geometry, spray pattern, and particle size distribution after the powder was sprayed using the UDS Powder Nasal Spray. Finally, the deposition patterns of the TFF AUG-3387C powder sprayed using the UDS Powder delivery system were studied using 3D-printed nasal replica casts based on the CT scans of an adult and a child. It is concluded that it is feasible to intranasally deliver mAbs as dry powders by transforming the mAbs into dry powders using thin-film freeze-drying and then spraying the powder using a powder nasal spray system.

Skin necrosis after intradermal injection of lyophilized exosome: A case report and a review of the literature.

BACKGROUND: Exosomes have gained attention for their potential in skin rejuvenation. Currently, most exosome products are available for topical administration, and the use of subdermal injection as a route of administration has not been approved. AIMS: The purpose of this case report is to describe a case of skin necrosis that occurred following an intradermal injection of lyophilized exosomes. MATERIALS AND METHODS: We hereby report a case of a middle-aged man who experienced adverse effects after receiving an intradermal injection of lyophilized exosomes. Multiple injections of an exosome product were administered to treat enlarged facial pores. Shortly after the injection, the patient felt pain and noticed several dark red bumps. Three days after injection, the lesions transformed into palpable, painful, non-blanchable purplish papules and nodules, accompanied by central, tiny crusted erosions. The residual product was injected into the upper arm using an intradermal method. Similar lesions also appeared, and a skin biopsy showed necrotic keratinocytes, leukocytoclastic vasculitis, and eccrine necrosis. RESULTS: There are few reports available regarding complications, especially those related to intradermal exosomes. These complications include multiple foreign-body granulomatous reactions at the injection sites. In our case, oral prednisolone was administered for a duration of 7 days. After the treatment, the lesions exhibited notable improvement, eventually leaving post-inflammatory hyperpigmentation. CONCLUSION: Utilizing exosomes through unapproved methods should be avoided due to the possibility of adverse reactions that could cause aesthetic issues.

Comparison of different drying methods for bergamot peel: Chemical and physicochemical properties.

This study examines the effectiveness of seven drying methods applied to bergamot peels, encompassing hot air, microwave, infrared-assisted microwave, freeze, infrared, sun, and oven drying. All samples exhibited moisture content and water activity levels within the acceptable range for dry foods. All methods effectively transformed the peels into powdered form, yielding comparable results. Each method offers distinct advantages and disadvantages, and the choice of method should be based on the desired properties of the final product. The highest ascorbic acid content was found in freeze-dried and hot air-dried samples (>400 mg/100 g), whereas sun-dried samples had the lowest (89.58 mg/100 g). Infrared-dried samples exhibited the highest levels of total phenolics and flavonoids (193.40 and 530.14 mg/100 g, respectively), attributed to reactions induced by elevated temperatures. The total carotenoids were higher in freeze-dried samples (54.12 mg/100 g) compared to other drying methods (<27 mg/100 g). Microwave-dried samples had the highest 5-hydroxymethylfurfural content (73.06 mg/100 g), and freeze-dried samples had the highest naringin content (1568.70 mg/100 g). Although infrared drying had good particle density, porosity, and fluidity, freeze-drying was the most effective, retaining the highest levels of bioactive compounds. Among the methods studied, freeze-drying is recommended due to its superior ability to preserve bioactive compounds. Infrared and infrared-assisted drying methods were suitable for recovering phenolics from bergamot waste, offering lower energy consumption and practical preservation of physicochemical properties. This study emphasizes the importance of selecting the appropriate drying method to ensure high-quality dried food and producing value-added products from bergamot waste, contributing to sustainable agriculture and waste reduction. PRACTICAL APPLICATION: This study demonstrates that infrared and freeze-drying are the most effective methods for producing high-quality bergamot peel samples with enhanced antioxidant properties. These findings hold promising implications for the food industry, offering a viable approach to preserve bergamot peels and their valuable attributes.

Assessment of freeze, continuous, and intermittent infrared drying methods for sliced persimmon.

Persimmons contribute positively to human health. Although off-season utilization typically presents a challenge due to permissions' perishable nature, it may become feasible through the implementation of appropriate drying methods. In this study, round sliced samples were dried to assess drying kinetics, modeling potential, color attributes, rehydration capacity, energy consumption (EC), cost index, and thermal properties. The fruits were subjected to distinct drying methodologies including freeze-drying, continuous infrared drying (300, 400, and 500 W), and intermittent infrared drying (PR = 1 [continuous], PR = 2 [30 s on-30 s off], and PR = 3 [20 s on-40 s off]). The duration of the drying process ranged from 40 to 390 min. It was determined that the most suitable models for depicting continuous and infrared drying kinetics of persimmon fruit were the Midilli et al. and Page models, whereas the Logarithmic model was identified as the optimal choice for characterization of freeze-drying kinetics. Assessment of EC revealed that both intermittent and continuous infrared drying methods incurred lower energy expenditure in comparison to the freeze-drying technique. Remarkably, throughout the course of the infrared drying processes, product surface temperatures varied between 106.33 and 22.65°C across different treatments. Despite its high EC, it has been found that high-quality products are produced by freeze-drying. However, infrared and intermittent infrared applications can be a low energy cost and feasible method for drying persimmon with a shorter duration. PRACTICAL APPLICATION: Persimmon is an important fruit with high nutritional value. However, as with many fresh products, they have a short shelf life. Within the scope of this research, three different drying methodologies were employed in the desiccation of persimmon specimens, and the impact of these methodologies on the overall qualitative attributes of the persimmon product was investigated. Despite its elevated energy consumption, the freeze-drying approach was found to yield high-quality products. Moreover, it was discerned that infrared drying represented a viable and expeditious alternative for drying the fruit, particularly when executed intermittently.

Development of favipiravir dry powders for intranasal delivery: An integrated cocrystal and particle engineering approach via spray freeze drying.

The therapeutic potential of pharmaceutical cocrystals in intranasal applications remains largely unexplored despite progressive advancements in cocrystal research. We present the application of spray freeze drying (SFD) in successful fabrication of a favipiravir-pyridinecarboxamide cocrystal nasal powder formulation for potential treatment of broad-spectrum antiviral infections. Preliminary screening via mechanochemistry revealed that favipiravir (FAV) can cocrystallize with isonicotinamide (INA), but not nicotinamide (NCT) and picolinamide (PIC) notwithstanding their structural similarity. The cocrystal formation was characterized by differential scanning calorimetry, Fourier-transform infrared spectroscopy, and unit cell determination through Rietveld refinement of powder X-ray analysis. FAV-INA crystalized in a monoclinic space group P21/c with a unit cell volume of 1223.54(3) Å3, accommodating one FAV molecule and one INA molecule in the asymmetric unit. The cocrystal was further reproduced as intranasal dry powders by SFD, of which the morphology, particle size, in vitro drug release, and nasal deposition were assessed. The non-porous flake shaped FAV-INA powders exhibited a mean particle size of 19.79 ± 2.61 µm, rendering its suitability for intranasal delivery. Compared with raw FAV, FAV-INA displayed a 3-fold higher cumulative fraction of drug permeated in Franz diffusion cells at 45 min (p = 0.001). Dose fraction of FAV-INA deposited in the nasal fraction of a customized 3D-printed nasal cast reached over 80 %, whereas the fine particle fraction remained below 6 % at a flow rate of 15 L/min, suggesting high nasal deposition whilst minimal lung deposition. FAV-INA was safe in RPMI 2650 nasal and SH-SY5Y neuroblastoma cells without any in vitro cytotoxicity observed. This study demonstrated that combining the merits of cocrystallization and particle engineering via SFD can propel the development of advanced dry powder formulations for intranasal drug delivery.

Optimización del proceso de liofilización de pulpa de maracuyá: efecto de diferentes aglomerantes en la cinéticade secado y características del producto final / Optimization of the passion pulp freeze-drying process: effect of differentbinders on drying kinetics and characteristics of the final product

Introducción: El estudio se centró en obtener pulpa liofi-lizada de maracuyá manteniendo su calidad sensorial y nu-tracéutica. Objetivo: Se evaluaron diferentes concentraciones deaglomerantes en propiedades físico-químicas, solubilidad, co-lor, vitamina C y polifenoles. Material y métodos: Se examinó la cinética de secado porliofilización en un diseño factorial 3x3, los aglomerantes (gomaarábiga, almidón de arroz, pectina) y sus concentraciones im-pactaron fenoles totales, vitamina C, color y solubilidad. Resultados: Destacaron la goma arábiga al 1.5% y la pec-tina al 1.0% para preservar sabor y color, y la pectina al0.75% mostró alta velocidad de secado. Conclusión: La goma arábiga sobresalió en fenoles tota-les, color y solubilidad, mientras que la pectina conservó me-jor la vitamina C.(AU)

Introduction: The study focused on obtaining freeze-dried passion fruit pulp while maintaining its sensorial and nu-tritional quality. Objective: Different concentrations of binders were eval-uated for physical-chemical properties, solubility, color, vita-min C and polyphenols. Methodology: The freeze-drying kinetics were examinedin a 3x3 factorial design, the binders (gum arabic, rice starch,pectin) and their concentrations impacted total phenols, vita-min C, color and solubility. Results: They highlighted gum arabic at 1.5% and pectinat 1.0% to preserve flavor and color, and pectin at 0.75%showed high drying speed. Conclusion: Gum Arabic excels in total phenols, color andsolubility, while pectin preserves vitamin C better.(AU)

Antibacterial and antifungal activities of natural deep eutectic solvents.

The increasing antibiotic resistance towards a panel of microorganisms is one of the public health concerns. For this reason, the search for alternatives to the widely used antibiotic has been undertaken. In the era of sustainable chemistry, deep eutectic solvents (DESs) have emerged as promising antimicrobial agents. These solvents possess several advantages such as low volatility, low flammability, ease of preparation, and typically low cost of production. These properties make DES suitable for various applications, including extraction of biomolecules and preparation of cosmetics. Natural DESs (NADESs) are special category of DESs prepared from natural sources, which matched the recent trends of leaning back to nature, and decreasing dependence on synthetic precursors. NADES can be prepared by heating and stirring, freeze-drying, evaporation, grinding, and ultrasound-assisted and microwave-assisted synthesis. Utilizing NADESs as an alternative to traditional antibiotics, which become ineffective over time due to bacterial resistance, holds great promise for these reasons. This review aims to discuss the antimicrobial properties of multiple NADESs, including antibacterial and antifungal activities. To the best of our knowledge, this review is the first literature survey of the antimicrobial activities of NADESs. KEY POINTS: • Natural deep eutectic solvents are promising antimicrobial alternative to antibiotics • NADES holds high potential for their activity against bacterial resistance • NADES have also substantial antifungal activities.