Effect of the addition of Chachafruto flour on the stability of oil-in-water emulsions and the physicochemical properties of spray-drying microcapsules.

This study aimed to assess the suitability of Chachafruto flour (CHF) as a stabilizing agent for an oil-in-water emulsion and its impact on the physicochemical properties of the emulsion after spray drying. Emulsions with varying CHF concentrations (2 %, 3 %, and 4 %) were prepared and compared to a control. The results from the creaming index and particle size (emulsion) analyses indicated that the highest emulsion stability was achieved with 4 %CHF, attributed to its protein content (20.5 %). The encapsulates exhibited spherical and rough surface morphologies but without holes on the surface. Low moisture content (MC < 5 %) and water activity (aw < 0.2) were associated with powder stability. The encapsulates added with CHF showed good reconstitution properties. FTIR confirmed the absence of chemical interactions during the encapsulation process, contributing to the stability. Furthermore, the addition of CHF improved the thermal stability of the encapsulates. This study represents the first investigation on the emulsifying potential of Chachafruto flour.

Microencapsulation of Extracts of Strawberry (Fragaria vesca) By-Products by Spray-Drying Using Individual and Binary/Ternary Blends of Biopolymers.

Valorization of agricultural and food by-products (agri-food waste) and maximum utilization of this raw material constitute a highly relevant topic worldwide. Agri-food waste contains different types of phytochemical compounds such as polyphenols, that display a set of biological properties, including anti-inflammatory, chemo-preventive, and immune-stimulating effects. In this work, the microencapsulation of strawberry (Fragaria vesca) plant extract was made by spray-drying using individual biopolymers, as well as binary and ternary blends of pectin, alginate, and carrageenan. The microparticle morphologies depended on the formulation used, and they had an average size between 0.01 µm and 16.3 µm considering a volume size distribution. The encapsulation efficiency ranged between 81 and 100%. The kinetic models of Korsmeyer-Peppas (R2: 0.35-0.94) and Baker-Lonsdale (R2: 0.73-1.0) were fitted to the experimental release profiles. In general, the releases followed a "Fickian Diffusion" mechanism, with total release times varying between 100 and 350 (ternary blends) seconds. The microparticles containing only quercetin (one of the main polyphenols in the plant) showed higher antioxidant power compared to the extract and empty particles. Finally, the addition of the different types of microparticles to the gelatine (2.7 mPa.s) and to the aloe vera gel (640 mPa.s) provoked small changes in the viscosity of the final gelatine (2.3 and 3.3 mPa.s) and of the aloe vera gel (621-653 mPa.s). At a visual level, it is possible to conclude that in the gelatine matrix, there was a slight variation in color, while in the aloe vera gel, no changes were registered. In conclusion, these microparticles present promising characteristics for food, nutraceutical, and cosmetic applications.

Absolute oral bioavailability of milvexian spray-dried dispersion formulation under fasted and fed conditions in healthy adult participants: An intravenous microtracer approach.

Milvexian is an oral, small-molecule factor XIa inhibitor being developed to prevent thromboembolic events. This study assessed the absolute bioavailability (F) of milvexian following single doses of milvexian spray-dried dispersion (SDD) formulation under fed and fasted conditions, and milvexian solution, in healthy adult participants using an intravenous microtracer approach. This was a phase I, open-label, partially randomized, 4-sequence, 5-period crossover study. After fasting for ≥10 h, participants received milvexian 200-mg oral solution with a 100-µg 14C milvexian intravenous microtracer at the time of maximum observed plasma concentration. Following a 3-day washout, participants were randomized to 1 of 4 milvexian SDD treatment sequences in a crossover fashion: 25 mg fasted, 25 mg fed, 200 mg fasted, or 200 mg fed. Pharmacokinetic data were collected up to 72 h postdose. Seventeen participants were dosed, and 14 completed treatment. Under fasted conditions, milvexian F was ~100%, 58.2%, and 54.2% following administration of the oral solution, 25 mg SDD, and 200 mg SDD, respectively. Under fed conditions, milvexian F following 25 mg and 200 mg SDD was 44.3% and 75.6%, respectively. The milvexian SDD formulation at 25 mg and 200 mg resulted in similar F in a fasted state; under fed conditions, milvexian F decreased at 25 mg and increased at 200 mg. These findings clarify pharmacokinetic-related gaps observed in previous studies.

Characteristics of pomegranate (Punica granatum L.) peel polyphenols encapsulated with whey protein isolate and ß-cyclodextrin by spray-drying.

Pomegranate peel polyphenols (PPPs) are recognized as promising food additives due to their diverse bioactivities; however, their application is limited by poor stability. To address this critical issue, three types of PPPs microcapsules were prepared using ß-cyclodextrin (CD), whey protein isolate (WPI), and a composite material of CD-WPI through ultrasound treatment (US). Results revealed that ultrasound treatment can enhance the PPPs-wall material interaction, as evidenced by MD simulations. The encapsulation efficiency of CD-WPI-PPPs was 93.73 %, which was significantly higher than that of CD-PPPs and WPI-PPPs (p < 0.05). The degradation rate constant of CD-WPI-PPPs was reduced by 95.83 %, and its t1/2 was extended by 23-fold compared to that of unencapsulated PPPs. Furthermore, CD-WPI-PPPs exhibited greater DPPH scavenging activity and inhibited polyphenol release during oral and gastric digestion while promoting release during intestinal digestion. These outcomes were attributed to enhanced integrity and interactions between PPPs and composite materials in the microcapsules formed through ultrasound treatment, as supported by SEM images and FT-IR spectra. Consequently, the application of US in the preparation of PPPs microcapsules presents a promising strategy for developing natural nutrient additives for food applications, thereby enhancing the functional properties of food products.

An aerosol nanocomposite microparticle formulation using rifampicin-cyclodextrin inclusion complexes for the treatment of pulmonary diseases.

Rifampicin (RIF) is commonly used in the treatment of tuberculosis (TB), a bacterium that currently infects one fourth of the world's population. Despite the effectiveness of RIF in treating TB, current RIF treatment regimens require frequent and prolonged dosing, leading to decreased patient compliance and, ultimately, increased mortality rates. This project aims to provide an alternative to oral RIF by means of an inhalable spray-dried formulation. TB uses alveolar macrophages to hide and replicate until the cells rupture, further spreading the bacteria. Therefore, delivering RIF directly to the lungs can increase the drug concentration at the site of infection while reducing off-site side effects. Cyclodextrin (CD) was used to create a RIF-CD inclusion complex to increase RIF solubility and biodegradable RIF-loaded NP (RIF NP) were developed to provide sustained release of RIF. RIF NP and RIF-CD inclusion complex were spray dried to form a dry powder nanocomposite microparticles (nCmP) formulation (RIF-CD nCmP). RIF-CD nCmP displayed appropriate aerosol dispersion characteristics for effective deposition in the alveolar region of the lungs (4.0 µm) with a fine particle fraction of 89 %. The nCmP provided both a burst release of RIF due to the RIF-CD complex and pH-sensitive release of RIF due to the RIF NP incorporated into the formulation. RIF-CD nCmP did not adversely affect lung epithelial cell viability and RIF NP were able to effectively redisperse from the nCmP after spray drying. These results suggest that RIF-CD nCmP can successfully deliver RIF to the site of TB infection while providing both immediate and sustained release of RIF. Overall, the RIF-CD nCmP formulation has the potential to improve the efficacy for the treatment of TB.

Spray drying of a zinc complexing agent for inhalation therapy of pulmonary fibrosis.

Pulmonary fibrosis, a disabling lung disease, results from the fibrotic transformation of lung tissue. This fibrotic transformation leads to a deterioration of lung capacity, resulting in significant respiratory distress and a reduction in overall quality of life. Currently, the frontline treatment of pulmonary fibrosis remains limited, focusing primarily on symptom relief and slowing disease progression. Bacterial infections with Pseudomonas aeruginosa are contributing to a severe progression of idiopathic pulmonary fibrosis. Phytic acid, a natural chelator of zinc, which is essential for the activation of metalloproteinase enzymes involved in pulmonary fibrosis, shows potential inhibition of LasB, a virulence factor in P. aeruginosa, and mammalian metalloproteases (MMPs). In addition, phytic acid has anti-inflammatory properties believed to result from its ability to capture free radicals, inhibit certain inflammatory enzymes and proteins, and reduce the production of inflammatory cytokines, key signaling molecules that promote inflammation. To achieve higher local concentrations in the deep lung, phytic acid was spray dried into an inhalable powder. Challenges due to its hygroscopic and low melting (25 °C) nature were mitigated by converting it to sodium phytate to improve crystallinity and powder characteristics. The addition of leucine improved aerodynamic properties and reduced agglomeration, while mannitol served as carrier matrix. Size variation was achieved by modifying process parameters and were evaluated by tools such as the Next Generation Impactor (NGI), light diffraction methods, and scanning electron microscopy (SEM). An inhibition assay for human MMP-1 (collagenase-1) and MMP-2 (gelatinase A) allowed estimation of the biological effect on tissue remodeling enzymes. The activity was also assessed with respect to inhibition of bacterial LasB. The formulated phytic acid demonstrated an IC50 of 109.7 µg/mL for LasB with viabilities > 80 % up to 188 µg/mL on A549 cells. Therefore, inhalation therapy with phytic acid-based powder shows promise as a treatment for early-stage Pseudomonas-induced pulmonary fibrosis.

Inhibition of influenza virus infection in mice by pulmonary administration of a spray dried antiviral drug.

Increasing resistance to antiviral drugs approved for the treatment of influenza urges the development of novel compounds. Ideally, this should be complemented by a careful consideration of the administration route. 6'siallyllactosamine-functionalized ß-cyclodextrin (CD-6'SLN) is a novel entry inhibitor that acts as a mimic of the primary attachment receptor of influenza, sialic acid. In this study, we aimed to develop a dry powder formulation of CD-6'SLN to assess its in vivo antiviral activity after administration via the pulmonary route. By means of spray drying the compound together with trileucine, a dispersion enhancer, we created a powder that retained the antiviral effect of the drug, remained stable under elevated temperature conditions and performed well in a dry powder inhaler. To test the efficacy of the dry powder drug against influenza infection in vivo, infected mice were treated with CD-6'SLN using an aerosol generator that allowed for the controlled administration of powder formulations to the lungs of mice. CD-6'SLN was effective in mitigating the course of the disease compared to the control groups, reflected by lower disease activity scores and by the prevention of virus-induced IL-6 production. Our data show that CD-6'SLN can be formulated as a stable dry powder that is suitable for use in a dry powder inhaler and is effective when administered via the pulmonary route to influenza-infected mice.

Surface Solid Dispersion of Ketoconazole on Trehalose Dihydrate using Spray Drying to Achieve Enhanced Dissolution Rate.

Ketoconazole (K) is a poorly water-soluble drug that faces significant challenges in achieving therapeutic efficacy. This study aimed to enhance the dissolution rate of ketoconazole by depositing spray-dried ketoconazole (SK) onto the surface of ground trehalose dihydrate (T) using spray drying. Ketoconazole-trehalose surface solid dispersions (SKTs) were prepared in ratios of 1:1 (SK1T1), 1:4 (SK1T4), and 1:10 (SK1T10), and characterized them using particle size analysis, scanning electron microscopy, powder X-ray diffraction, and in vitro dissolution studies. Results showed that the dissolution rates of the dispersions were significantly higher than those of pure ketoconazole, with the 1:10 ratio showing the highest dissolution rate. The improved dissolution was attributed to the formation of a new crystalline phase and better dispersion of ketoconazole particles. These findings suggest that the surface solid dispersion approach could be a valuable method for enhancing the bioavailability of poorly water-soluble drugs.

Stable and inhalable powder formulation of mRNA-LNPs using pH-modified spray-freeze drying.

A powder formulation for mucosal administration of mRNA-encapsulated lipid nanoparticles (mRNA-LNPs) is expected to be useful for respiratory diseases. Although freeze-drying is widely used to obtain solid formulations of mRNA-LNPs, highly hydrosoluble cryoprotectants, such as sucrose are necessary. However, sucrose is not a suitable excipient for inhalation powders because of its hygroscopic and deliquescence properties. Spray freeze-drying (SFD) is a method to produce inhalable powder formulation. In this study, we prepared inhalable powder formulations of mRNA-LNPs without deliquescence excipients using pH-modified SFD, which strengthens the interaction between mRNA and ionizable lipids of LNPs by acidic pH modifier, leading to retention of the encapsulated structure of mRNA-LNPs even after SFD. Powdered mRNA-LNPs were suitable for inhalation, and mRNA was encapsulated in LNPs after SFD. The mRNA encapsulation efficiency and mRNA transfection efficiency of pH-modified SFD-mediated powdered mRNA-LNPs were higher than those of conventional SFD, although they were significantly lower than those of liquid intact mRNA-LNPs. However, after long-term storage, the powdered formulation of the mRNA-LNPs exhibited higher mRNA transfection efficiency than liquid mRNA-LNP. Powdered mRNA-LNPs also exerted their function in air-liquid interface cultivation and in vivo intratracheal administration. Collectively, the powder formulation of mRNA-LNPs especially prepared by SFD is expected to be applied for dry powder inhalers.

Effects of spray drying on the content of crystal proteins of Bacillus thuringiensis and the protection by organic and inorganic auxiliaries.

Spray drying is an important industrial method for the preparation of B. thuringiensis powder from fermentation liquor. The effect of spray drying on the crystal proteins, however, has not been reported in the literature so far. The present study systematically investigated the effect of inlet air temperature, outlet air temperature, atomizing air pressure and additives (including organic and inorganic auxiliaries) on the thermal destruction of crystal proteins of B. thuringiensis. The results indicated that the content of crystal proteins of B. thuringiensis powder decreased with increased inlet air temperature, outlet air temperature and atomising air pressure. The pseudo-z values for inlet air temperature, outlet air temperature and atomizing air pressure were 826.4 â„ƒ, 204.0 â„ƒ and 4.74 MPa, respectively. Among them, the outlet air temperature was a major parameter influencing the thermal destruction of crystal proteins, therefore, the decrease of the outlet air temperature was beneficial to increase the protein content in powder. Although the spray drying had an adverse effect on crystal proteins, the crystal protein content in spray-dried powder approached that in freeze-dried powder when the inlet air temperature of 165 â„ƒ, outlet air temperature of 70 â„ƒ and atomizing air pressure of 0.15 MPa were employed. The addition of some organic and inorganic auxiliaries to fermentation liquor can protect the crystal proteins from heat damage.

Development of a proliposomal pretomanid dry powder inhaler as a novel alternative approach for combating pulmonary tuberculosis.

Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) continue as public health concerns. Inhaled drug therapy for TB has substantial benefits in combating the causal agent of TB (Mycobacterium tuberculosis). Pretomanid is a promising candidate in an optional combined regimen for XDR-TB. Pretomanid has demonstrated high potency against M. tuberculosis in both the active and latent phases. Conventional spray drying was used to formulate pretomanid as dry powder inhalers (DPIs) for deep lung delivery using a proliposomal system with a trehalose coarse excipient to enhance the drug solubility. Co-spray drying with L-leucine protected hygroscopic trehalose in formulations and improved powder aerosolization. Higher amounts of L-leucine (40-50 % w/w) resulted in the formation of mesoporous particles with high percentages of drug content and entrapment efficiency. The aerosolized powders demonstrated both geometric and median aerodynamic diameters < 5 µm with > 90 % emitted dose and > 50 % fine particle fraction. Upon reconstitution in simulated physiological fluid, the proliposomes completely converted to liposomes, exhibiting suitable particle sizes (130-300 nm) with stable colloids and improving drug solubility, leading to higher drug dissolution compared to the drug alone. Inhalable pretomanid showed higher antimycobacterial activity than pretomanid alone. The formulations were safe for all broncho-epithelial cell lines and alveolar macrophages, thus indicating their potential suitability for DPIs targeting pulmonary TB.

Effect of processing and formulation factors on Catalase activity in tablets.

The manufacturing of tablets containing biologics exposes the biologics to thermal and shear stresses, which are likely to induce structural changes (e.g., aggregation and denaturation), leading to the loss of their activity. Saccharides often act as stabilizers of proteins in formulations, yet their stabilizing ability throughout solid oral dosage processing, such as tableting, has been barely studied. This work aimed to investigate the effects of formulation and process (tableting and spray-drying) variables on catalase tablets containing dextran, mannitol, and trehalose as potential stabilizers. Non-spray-dried and spray-dried formulations were prepared and tableted (100, 200, and 400 MPa). The enzymatic activity, number of aggregates, reflecting protein aggregation and structure modifications were studied. A principal component analysis was performed to reveal underlying correlations. It was found that tableting and spray-drying had a notable negative effect on the activity and number of aggregates formed in catalase formulations. Overall, dextran and mannitol failed to preserve the catalase activity in any unit operation studied. On the other hand, trehalose was found to preserve the activity during spray-drying but not necessarily during tableting. The study demonstrated that formulation and process variables must be considered and optimized together to preserve the characteristics of catalase throughout processing.

Microencapsulation of natural products using spray drying; an overview.

AIMS: This study examines microencapsulation as a method to enhance the stability of natural compounds, which typically suffer from inherent instability under environmental conditions, aiming to extend their application in the pharmaceutical industry. METHODS: We explore and compare various microencapsulation techniques, including spray drying, freeze drying, and coacervation, with a focus on spray drying due to its noted advantages. RESULTS: The analysis reveals that microencapsulation, especially via spray drying, significantly improves natural compounds' stability, offering varied morphologies, sizes, and efficiencies in encapsulation. These advancements facilitate controlled release, taste modification, protection from degradation, and extended shelf life of pharmaceutical products. CONCLUSION: Microencapsulation, particularly through spray drying, presents a viable solution to the instability of natural compounds, broadening their application in pharmaceuticals by enhancing protection and shelf life.

Advantages of Spray Drying over Freeze Drying: A Comparative Analysis of Lonicera caerulea L. Juice Powders-Matrix Diversity and Bioactive Response.

The study investigated the impact of Lonicera caerulea L. juice matrix modification and drying techniques on powder characteristics. The evaluation encompassed phenolics (514.7-4388.7 mg/100 g dry matter), iridoids (up to 337.5 mg/100 g dry matter), antioxidant and antiglycation capacity, as well as anti-ageing properties of powders produced using maltodextrin, inulin, trehalose, and palatinose with a pioneering role as a carrier. Spray drying proved to be competitive with freeze drying for powder quality. Carrier application influenced the fruit powder properties. Trehalose protected the phenolics in the juice extract products, whereas maltodextrin showed protective effect in the juice powders. The concentrations of iridoids were influenced by the matrix type and drying technique. Antiglycation capacity was more affected by the carrier type in juice powders than in extract products. However, with carrier addition, the latter showed approximately 12-fold higher selectivity for acetylcholinesterase than other samples. Understanding the interplay between matrix composition, drying techniques, and powder properties provides insights for the development of plant-based products with tailored attributes, including potential health-linked properties.

Effect of gastrointestinal resistant encapsulate matrix on spray dried microencapsulated Lacticaseibacillus rhamnosus GG powder and its characterization.

This study investigated spray drying a method for microencapsulating Lacticaseibacillus rhamnosus GG using a gastrointestinal resistant composite matrix. An encapsulate composite matrix comprising green banana flour (GBF) blended with maltodextrin (MD) and gum arabic (GA). The morphology of resulted microcapsules revealed a near-spherical shape with slight dents and no surface cracks. Encapsulation efficiency and product yield varied significantly among the spray-dried microencapsulated probiotic powder samples (SMPPs). The formulation with the highest GBF concentration (FIV) exhibited maximum post-drying L. rhamnosus GG viability (12.57 ± 0.03 CFU/g) and best survivability during simulated gastrointestinal digestion (9.37 ± 0.05 CFU/g). Additionally, glass transition temperature (Tg) analysis indicated good thermal stability of SMPPs (69.3 - 92.9 ℃), while Fourier Transform infrared (FTIR) spectroscopy confirmed the structural integrity of functional groups within microcapsules. The SMPPs characterization also revealed significant variation in moisture content, water activity, viscosity, and particle size. Moreover, SMPPs exhibited differences in total phenolic and flavonoid, along with antioxidant activity and color values throughout the study. These results suggested that increasing GBF concentration within the encapsulating matrix, while reducing the amount of other composite materials, may offer enhanced protection to L. rhamnosus GG during simulated gastrointestinal conditions, likely due to the gastrointestinal resistance properties of GBF.

Spray Drying of Bacterial Membrane Vesicles for Vaccine Delivery.

Extracellular vesicles are nanosized lipid-bilayered spheres secreted from every living cell and they serve physiological and pathophysiological functions. Bacterial membrane vesicles are shed from both Gram-negative and Gram-positive bacteria and harbor many virulence factors, nuclear material, polysaccharides, proteins, and antigenic determinants, which are essential for immune recognition and evasion. Hence, bacterial membrane vesicles are very promising vaccine candidates. Spray drying is a well-established pharmaceutical technique to produce inhalable dry powders with enhanced stability for formulations of vaccines. In this chapter, we illustrate general guidelines for spray drying of bacterial extracellular vesicles to improve their stability without compromising their immunogenic protective effect. We discuss some of the most important experiments to characterize the generated spray-dried bacterial membrane vesicle powder vaccine.

Impact of plasmolysis process on the enrichment of brewer's spent yeast biomass with vitamin D3 by biosorption followed by spray-drying process.

Vitamin D3(cholecalciferol)plays a crucial role in various physiological processes. However, vitamin D3 deficiency is a major public health problem affecting millions of people. Therefore, it is important to develop effective strategies that ensure the protection and stability of this important vitamin for food supplementation and fortification. This work aimed to impregnate intact and plasmolyzedSaccharomyces pastorianus brewer's yeast biomass with cholecalciferol using a biosorption process followed by spray drying to characterize the obtained material in terms of morphology, average particle size, zeta potential, moisture, water activity, FT-IR, and the stability of the encapsulated vitamin during the drying and storage process. Plasmolysis proved to be an effective method for improving the biosorption efficiency, retention during spray drying, and stability of vitamin D3. In addition, this process promoted an increase in cell size, which favored the dispersion stability of the system, as evidenced by the zeta potential values. These results contribute to the understanding of a new method for delivering this vitamin that conforms to environmentally conscious practices.

Impact of wall materials and DHA sources on the release, digestion and absorption of DHA microcapsules: Advancements, challenges and future directions.

Docosahexaenoic acid (DHA), an essential omega-3 fatty acid, offers significant health benefits but faces challenges such as distinct odor, oxidation susceptibility, and limited intestinal permeability, hindering its broad application. Microencapsulation, widely employed, enhances DHA performance by facilitating controlled release, digestion, and absorption in the gastrointestinal tract. Despite extensive studies on DHA microcapsules and related delivery systems, understanding the mechanisms governing encapsulated DHA release, digestion, and absorption, particularly regarding the influence of wall materials and DHA sources, remains limited. This review starts with an overview of current techniques commonly applied for DHA microencapsulation. It then proceeds to outline up-to-date advances in the release, digestion and absorption of DHA microcapsules, highlighting the roles of wall materials and DHA sources. Importantly, it proposes strategies for overcoming challenges and exploiting opportunities to enhance the bioavailability of DHA microcapsules. Notably, spray drying dominates DHA microencapsulation (over 90 % usage), while complex coacervation shows promise for future applications. The combination of proteins and carbohydrates or phospholipids as wall material exhibits potential in controlling release and digestion of DHA microcapsules. The source of DHA, particularly algal oil, demonstrates higher lipid digestibility and absorptivity of free fatty acids (FFAs) than fish oil. Future advancements in DHA microcapsule development include formulation redesign (e.g., using plant proteins as wall material and algal oil as DHA source), technique optimization (such as co-microencapsulation and pre-digestion), and creation of advanced in vitro systems for assessing DHA digestion and absorption kinetics.

Physical and Functional Properties of Powders Obtained during Spray Drying of Cyani flos Extracts.

Edible flowers are a potential source of bioactive ingredients and are also an area of scientific research. Particularly noteworthy are Cyani flos, which have a wide range of uses in herbal medicine. The below study aimed to investigate the influence of selected soluble fiber fractions on the selected properties of physical and biochemical powders obtained during spray drying a water extract of Cyani flos. The drying efficiency for the obtained powders was over 60%. The obtained powders were characterized by low moisture content (≤4.99%) and water activity (≤0.22). The increase in the addition of pectin by the amount of 2-8% in the wall material resulted in a decrease in hygroscopicity, water solubility, and protection of flavonoids and anthocyanins both before and after digestion in the tested powders in comparison to the sample with only inulin as a carrier. Additionally, it was noted that all samples were characterized by high bioaccessibility when determining antioxidant properties and xanthine oxidase inhibition.

ß-Lactoglobulin-based amorphous solid dispersions: A graphical review on the state-of-the-art.

Proteins have recently caught attention as potential excipients for amorphous solid dispersions (ASDs) to improve oral bioavailability of poorly water-soluble drugs. Notably, the studies have highlighted whey protein isolates, particularly ß-lactoglobulin (BLG), as promising candidates in amorphous stabilization, dissolution and solubility enhancement, achieving drug loadings of 50 wt% and higher. Consequently, investigations into the mechanisms underlying the solid-state stabilization of amorphous drugs and the enhancement of drug solubility in solution have been conducted. This graphical review provides a comprehensive overview of recent findings concerning BLG-based ASDs. Firstly, the dissolution performance of BLG-based ASDs is compared to more traditional polymer-based ASDs. Secondly, the drug loading onto BLG and the resulting amorphous stabilization mechanisms is summarized. Thirdly, interactions between BLG and drug molecules in solution are described as the mechanisms governing the improvement of drug solubility. Lastly, we outline the impact of the spray drying process on the secondary structure of BLG, and the resulting differences in amorphous stabilization and drug dissolution performance between α-helix-rich and ß-sheet-rich BLG-based ASDs.