Search Results (308)

Background/Objectives: Cannabidiol (CBD) has emerged as a potential therapeutic agent for respiratory disorders, including asthma and chronic obstructive pulmonary disease. However, its clinical translation via pulmonary delivery is limited by poor aqueous solubility, chemical instability, and low local bioavailability. This study aimed to develop and optimize a sodium stearate (NaSt)-based spray-dried dry powder inhaler (DPI) formulation to enhance the aerosol performance, dissolution, and storage stability of CBD. Methods: CBD microparticles were prepared by spray drying using NaSt as the primary excipient. The feed preparation method, spray-drying parameters, and CBD:NaSt ratios were systematically optimized. The resulting powders were evaluated for aerodynamic properties using cascade impaction, dissolution behavior in simulated lung fluid, solid-state characteristics, and accelerated stability under stress conditions. Results: The optimized formulation, SD-4, a spray-dried CBD:NaSt formulation prepared at a 20:80 weight ratio using Process B, demonstrated excellent aerosolization performance, with a fine particle fraction (FPF) exceeding 50% and a mass median aerodynamic diameter (MMAD) of 5.08 ± 0.1 μm. Dissolution testing revealed more than a three-fold increase in drug release compared with raw CBD, attributed to amorphous dispersion within the NaSt matrix and surfactant-induced micellization. Accelerated stability studies confirmed improved retention of the amorphous state and drug content, while antioxidant incorporation further reduced oxidative degradation. Conclusions: The NaSt-based spray-dried formulation significantly improved aerosol deposition efficiency, dissolution rate, and physicochemical stability of CBD. This formulation strategy may provide a promising platform for pulmonary delivery of poorly water-soluble compounds. Full article

The formulation of rhizobial bioinoculants remains a critical bottleneck for the large-scale deployment of biological nitrogen fixation in sustainable agriculture, mainly due to limitations in the stability and viability of conventional liquid products. In this study, a spray-drying-based process was developed and optimized to produce a stable and functional bioinoculant using Ensifer meliloti Rm8530, an EPS II–producing strain with enhanced stress tolerance. Strain robustness was evaluated through thermal and osmotic stress assays, together with growth performance across relevant temperature and pH ranges. Six carrier-based formulations combining polysaccharides and proteins were then tested under controlled spray-drying conditions. Process performance was assessed in terms of powder recovery, residual moisture, bacterial survival, yield, and storage stability over 16 weeks. The morphological integrity of spray-dried particles and rehydrated cells was analyzed by scanning electron microscopy. The biological functionality of selected formulations was subsequently validated in planta using alfalfa as a host model. Among the formulations tested, a mixed alginate–gum Arabic matrix showed the best overall balance between process efficiency, post-drying viability, long-term stability, and symbiotic performance. Spray-dried cells retained the ability to induce nodulation and support early plant responses under the conditions evaluated. These results demonstrate that spray drying, combined with appropriate strain selection and formulation design, constitutes a viable and scalable platform for producing stable, functional rhizobial bioinoculants. Full article

Background/Objectives: Reproducible evaluation of aerosol dispersibility remains a key challenge in the development of dry powder inhalers (DPIs), where small variations in particle cohesion, morphology, or device resistance can lead to large differences in aerodynamic performance. In passive DPIs, the forces required for powder fluidization and aerosolization arise from the interaction of patient inspiratory airflow with device geometry and must overcome strong interparticle cohesive forces to enable effective lung delivery. Cascade impaction is the gold standard for determining aerodynamic particle size distribution (APSD), but its low throughput and experimental burden limit its utility for systematic formulation and device screening. Prior studies have explored laser diffraction-based particle sizing under varying dispersion energies as indirect metrics of powder dispersibility. Here, we extend this approach by introducing a mathematically rigorous, distribution-based framework that applies the first-order Wasserstein distance (Earth Mover’s Distance) to quantify relative dispersibility with respect to a material-specific maximally dispersed reference state. Methods: Mannitol, trehalose, and inulin were spray-dried under matched conditions to generate model dry powders. Particle size distributions were measured by laser diffraction (Sympatec HELOS/R) using both a RODOS dry dispersion module to define a maximally dispersed reference state and an INHALER module to generate aerosols under clinically relevant dispersion conditions spanning multiple device resistances and pressure drops. For each condition, the Wasserstein-1 distance (W₁) was computed between cumulative volume-based size distributions obtained under reference and inhaler-based dispersion. Cascade impaction was used as an orthogonal method to characterize aerodynamic performance under a representative dispersion condition. Results: W₁ captured formulation-, device-, and flow-dependent differences in dispersibility that were not readily separable by visual inspection of particle size distributions alone. Crystalline mannitol exhibited the largest and most flow-rate-dependent W₁ values, whereas amorphous trehalose and polymeric inulin showed smaller W₁ values with distinct, non-monotonic pressure responses that depended on device resistance. W₁ qualitatively aligned with cascade impaction metrics, exhibiting a positive association with mass median aerodynamic diameter and an inverse association with fine particle fraction, while also demonstrating that efficient dose emission can occur despite incomplete deagglomeration. Conclusions: This study establishes the Wasserstein distance as a physically interpretable, formulation-agnostic metric for quantifying aerosol dispersibility relative to a material-specific reference state. This framework enables systematic comparison of dispersion efficiency across devices and operating conditions using standard laser diffraction data and provides a reproducible basis for mechanistic optimization of DPI formulations and inhaler designs. Full article

Background/Objectives: Tuberculosis (TB) remains a major global health threat. Current administration methods for anti-TB drugs, including oral or intravenous, suffer from systemic side effects, low lung distribution, and poor patient compliance. Dry powder inhalers (DPIs) offer a promising alternative. This study investigates the aerodynamic performance of co-spray-dried DPIs containing rifampin or pyrazinamide and amino acids by using machine learning. Methods: Firstly, 72 formulations were prepared by varying drug-amino acid combinations, molar ratios, and spray-drying parameters. Subsequently, the aerodynamic performance of all 72 formulations was evaluated using a Next Generation Impactor, and the solid-state characterizations of optimal DPIs were carried out. Finally, four machine learning (ML) models were successfully developed and were utilized to predict the fine particle dose (FPD), FPF, MMAD, and geometric standard deviation (GSD) of DPIs based on the high-quality in-house data above. Results: Key results showed that the aerodynamic performance of DPIs was highly dependent on the specific drug-amino acid combination, with rifampin-L-lysine acetate and pyrazinamide-L-leucine formulations achieving the highest fine particle fraction (FPF, 73.37%, 87.74%) and optimal mass median aerodynamic diameter (MMAD, 2.59 µm, 1.88 µm). Notably, XGBoost (v3.1.3) exhibited the best predictive performance, with R² values ranging from 0.894 to 0.991 in the testing set for the four prediction tasks. Meanwhile, SHapley Additive exPlanations (v0.50.0) was used for model interpretability analysis. The molecular weights and LogP of the drug and amino acid were identified as two of the most important features affecting the prediction of FPD, FPF, MMAD, and GSD. Conclusions: This work demonstrates the feasibility of ML in accelerating the development of inhalable spray-dried anti-TB drugs by enabling the prediction of DPI formulations. Full article

This study investigated the impact of pH adjustment and carrier type on the physicochemical properties, antioxidant activity, thermal stability, hygroscopicity, and particle size distribution of spray-dried model solutions and carrot juice formulations. Model systems were created at varying pH levels (3, 4, 6, 8, and 10) using water alone or with carriers such as octenyl succinic anhydride (OSA)-modified starch (O), trehalose (T), or a combination (OT in a 1:1 ratio at 9–10%). These systems were compared to carrot juice and formulations of carrot juice that included the same carriers. Spray drying was performed at 160 °C using constant feed flow and atomization conditions. In the liquid samples, we measured pH, dry matter, density, conductivity, and color parameters, while the bioactive compounds were analyzed in carrot juice systems. For the powders, we evaluated the dry matter content, color, particle size distribution, morphology, thermal stability, hygroscopicity, and antioxidant activity. Results showed that in model systems, dry matter, density, and conductivity were more affected by the carrier chemistry than pH. Formulations with OSA had lower pH and higher conductivity due to ionizable groups, while trehalose acted neutrally. OSA-trehalose mixtures yielded the highest solids content and stable properties across pH levels, with particle size (D₅₀ range of 18–21 µm) and morphology of the model powders remaining largely unaffected by pH. In carrot juice formulations, however, particle properties were pH-dependent. Acidic conditions (pH 3–4) led to agglomeration and broader size distributions (indicated by increased span values), while neutral to alkaline conditions produced smaller, more uniform particles with improved thermal stability. Neutral to alkaline conditions favored the formation of smaller, more homogeneous particles and improved thermal resistance. The carotenoid content in carrot juice powders increased from approximately 21–23 mg/100 g dry matter (d.m.) under acidic conditions to about 27–30 mg/100 g d.m. at pH 8–10, which was accompanied by higher ABTS antioxidant activity (around 6–9 mg Trolox equivalents (TE)/g d.m.). In contrast, the polyphenol content was highest at low pH levels (approximately 350–420 mg chlorogenic acid (CA)/100 g d.m.), corresponding to elevated DPPH scavenging activity and reducing power, both of which decreased under alkaline conditions. These findings indicate that pH levels and carrier choice significantly affect spray-dried powders. This highlights the importance of validating model system observations in complex food matrices. By adjusting pH and selecting suitable carriers, we can create powders with improved structures, stability, and antioxidant functionality, particularly in foods like carrot juice. Full article

Lower respiratory tract infections caused by Pseudomonas aeruginosa are a global concern. Patients with chronic lung diseases such as cystic fibrosis and non-cystic fibrosis bronchiectasis often do not receive adequate antibiotic delivery through conventional routes. P. aeruginosa employs several mechanisms, including biofilm formation and efflux pumps to limit the accumulation of bactericidal drug concentrations. Direct drug delivery to the lung epithelial lining fluid can increase antibiotic concentration and reduce treatment failure rates. This review discusses current research and developments in inhaled antibiotic formulations for treating P. aeruginosa infections. Recent studies on particle engineering for the dry powder inhalers of antibiotics emphasized three fundamental principles of development: micro, nano, and nano-in-microparticles. Carrier-free microparticles showed potential for high-dose delivery but suffered from poor aerosolization, which could be improved through a drug–drug combination. Amino acids in a co-spray-dried system improved powders’ aerodynamics and reduced moisture sensitivity while incorporating the chitosan/poly(lactic-co-glycolic acid) (PLGA)-modified release of the drug. Nano-in-microsystems, embedding lipid carriers, showed improved antibiofilm activity and controlled release. We also highlight emerging biologics, including antibacterial proteins/peptides, vaccines, bacteriophages, and probiotics. Research on antibiotics and biologics for inhalation suggests excellent safety profiles and encouraging efficacy for some formulations, including antimicrobial peptides and bacteriophage formulations. Further research on novel molecules and synergistic biologic combinations, supported by comprehensive animal lung safety investigations, will be required in future developments. Full article

Background/Objectives: This study developed a macitentan (MAC)–tadalafil (TAD) dry powder inhalation preparation using suspension-based spray drying to enhance pulmonary delivery and reduce systemic exposure to oral combination therapy in patients with pulmonary arterial hypertension (PAH). Methods: MAC–TAD composite powders were prepared by physically mixing or spray-drying aqueous ethanol suspensions at various MAC:TAD ratios. The lead M2-T8 was co-spray-dried with 5, 25, or 50% (w/w) L-leucine. Results: Spray-dried formulations exhibited narrower and more uniform particle size distributions (Dv50 2–6 µm; Dv90~10 µm) and higher emitted dose values than the physical mixtures. In the M2-T8 spray-dried formulation, TAD exhibited an elevated fine particle dose (FPD) (3073.45 ± 1312.30 μg), demonstrating improved aerosolization relative to the physical mixture, even outperforming the TAD-higher M1-T9 formulation (2896.83 ± 531.38 μg), suggesting that favorable interparticle adhesive interactions were developed during co-drying. The incorporation of 25% L-leucine produced the greatest improvement in dispersibility, increasing the FPD by ~31% for MAC and 17% for TAD, whereas excessive L-leucine (50%) reduced the aerosol performance. Powder X-ray diffraction and differential scanning calorimetry confirmed the retention of the MAC and TAD crystallinities, with L-leucine remaining either amorphous or partially crystalline. Conclusions: Suspension-based spray drying yielded MAC–TAD composite formulations with improved uniformity and aerosol performance. The optimized 2:8 formulation containing 25% L-leucine demonstrated the most efficient pulmonary deposition, supporting its potential as an inhaled combination therapy for the treatment of PAH. Full article

Araucaria angustifolia produces seeds known as Pinhão, which are valued for their nutritional composition and potential use in functional foods. This study investigated the production and characterization of spray-dried Pinhão extracts using inulin (E1) and polydextrose (E2) as carrier agents. The formulations were assessed for physicochemical composition, physical properties, rehydration behavior, morphology, phenolic profile, and mineral content. Spray drying resulted in yields of 67.7% (E1) and 60.6% (E2). E1 exhibited higher carbohydrate (37.02 g/100 g) and fiber contents (34.11 g/100 g), as well as lower moisture (1.35 g/100 g) and water activity (0.16), yielding powders with greater stability and lighter color. E2 demonstrated a superior rehydration performance, with higher wettability and dispersibility, attributed to the amorphous and hydrophilic nature of polydextrose. The matrix formed by inulin and polydextrose during spray drying was equally effective in preserving the low contents of phenolic compounds, demonstrating the suitability of the technique for stabilizing these heat-sensitive bioactive compounds. Only very low levels of phenolic compounds were detected in both samples, which is consistent with the naturally low phenolic content of the Pinhão almond. Mineral analysis showed greater calcium and magnesium retention in E1, whereas E2 contained higher levels of potassium, phosphorus, iron, and zinc. Overall, inulin enhanced powder stability and compactness, while polydextrose improved rehydration behavior and mineral preservation, supporting the potential application of Pinhão extract powders in functional and health-oriented food products. Full article

Background: Powdered mucilages are increasingly being used as natural excipients in pharmaceutical formulations, functioning as binders, disintegrants, thickeners, suspending agents, and film formers. Their swelling, viscosity-enhancing, and biocompatible properties also make them useful in controlled-release systems and tablet production. This study aimed to produce spray-dried Cydonia oblonga (CO) mucilage, examine how drying parameters influence yield, and determine its physicochemical and rheological characteristics to evaluate its suitability for pharmaceutical applications. Methods: Powdered CO mucilage was obtained by spray drying. The obtained powders were characterized on yield, particle size and morphology, moisture content, loss on drying, flow properties and swelling index. Results: The obtained powders show yields of 10.6–16.4%, particle sizes of 4.5–5.39 μm, and moisture contents of 2–3%. Their flowability is limited despite satisfactory angle of repose, Hausner ratio, and Carr index values, yet all powders exhibit excellent swelling properties. Conclusions: Model CM6 of the obtained powdered CO seeds hydrocolloid stands out as the best spray-dried hydrocolloid, combining high drying efficiency, low residual moisture, uniform particle formation, and excellent swelling capacity despite its limited flowability. These properties make it a strong candidate for use as a biopolymer or excipient in pharmaceuticals. Full article

Spray drying techniques are widely used in the pharmaceutical industry to produce fine drug powders with different properties depending on the route of administration. Process parameters play a vital role in the critical quality attributes of the final product. This review highlights the progress and challenges in modeling the spray-drying process, with a focus on pharmaceutical applications. Computational fluid dynamics (CFD) is a well-known method used for the modeling and numerical simulation of spray drying processes. However, owing to their limitations, including high computational costs, experimental validation, and limited accuracy under complex spray drying conditions. Machine learning (ML) models have recently emerged as integral tools for modeling/optimizing the spray drying process. Despite promising accuracy, ML models depend on high-quality data and may fail to predict the influence of new formulation or process parameters on the properties of the dried powder. This review outlines the shortcomings of CFD modeling in the spray drying process. A hybrid model combining ML and CFD models, emerging techniques such as the digital twin approach, transfer learning, and explainable AI (XAI) are also discussed. A hybrid model combining ML and CFD models is also discussed. ML is considered an emerging technique that could assist the spray drying process, and most importantly, the utilization of this method in pharmaceutical spray drying. Full article

This study evaluated the impact of the drying and carrier type on the physicochemical and functional properties of Ginkgo biloba L. and Clitoria ternatea L. extracts and their blends, at ratios of 1:1, 1:2, and 2:1 (w/w). Extracts were obtained using water as a green solvent and dried by freeze− or spray drying with maltodextrin or inulin. Powders were characterized for moisture content, water activity, color, polyphenol composition (HPLC–MS/MS), and antioxidant capacity (Folin–Ciocalteu, TEAC ABTS, FRAP). Spray−dried samples exhibited lower moisture content and water activity, while freeze-drying ensured higher polyphenol levels. The 1:1 (w/w) blend with inulin showed the most favorable balance between stability and antioxidant capacity, indicating synergistic effects. This formulation was selected for pilot-scale processing and encapsulated into hard gelatin capsules, which demonstrated rapid polyphenols release under simulated gastric conditions. The findings highlight the potential of spray-dried polyphenol-rich powders as standardized ingredients for immediate-release dietary supplements. Full article

Background. Inhalable monoclonal antibodies were explored as therapeutics for respiratory viral infections due to their high specificity, which, however, can become a drawback if virus mutational escape occurs. Serum-derived polyclonal antibodies for prophylaxis reflect the diverse response of the immune system, reducing susceptibility to virus mutations and targeting multiple epitopes. Objectives. The aim of this work was the development of inhalable powders containing serum of rats immunized against SARS-CoV-2. Methods & Results. In a preliminary screening, combinations of sugar and an amino acid outperformed single excipients in terms of retention of protein size and residual moisture content. Four formulations were further developed on neat and albumin-depleted serum: HPβCD/L-leucine in water, HPβCD/L-leucine in phosphate buffer (KP), trehalose/L-leucine in water and HPβCD/glycine in KP. These were subsequently evaluated for aerosol performance and protein stability. All spray-dried formulations afforded respirable particles (MMAD ≤ 5 µm, FPF 70–80%), with L-leucine reducing hygroscopicity and particle aggregation while improving aerosol dispersibility. Conclusions. Albumin did not positively affect aerodynamic properties but provided greater protection of immunoglobulin activity (approximately 80% and 90% in albumin-depleted and neat serum, respectively). Buffer selection had no remarkable impact on the considered parameters. L-leucine with HPβCD offered the best balance of aerodynamic performance and protein stabilization. Full article

Plant-based fermented coconut yogurt, valued for its functional properties, requires transformation into a shelf-stable powder, necessitating carriers to overcome particle stickiness and preserve probiotic viability. The objective of this study was to investigate the influence of polysaccharide carriers (maltodextrins DE 2, 10, and 19, and resistant dextrin) on processing efficiency, physicochemical stability, and lactic acid bacteria (LAB) viability. The feed, standardized to 15% total solids (initial LAB counts of 8.54 log CFU/g), was spray-dried at a 120 °C inlet temperature and a 65 °C outlet temperature. The drying condition reduced LAB viability by two log cycles regardless of the tested carriers. Maltodextrin DE 19 showed the highest powder yield, the lowest water activity, and a higher water solubility index. No significant differences in bulk density, pH, titratable acidity, and lactic acid content were observed among samples. Low-DE maltodextrins (DE 2 and 10) demonstrated significantly higher retention of sensitive malic and citric acids compared to DE 19. The current findings suggested that high-DE carriers provided beneficial effects on physical processing via kinetic shell formation, while low-DE carriers were able to protect against the loss of small organic acids. Overall, the study lays a foundation for spray-dried carrier development for coconut yogurt. Full article

Background/Objectives: Direct compression offers a cost-effective route for tablet manufacturing but is often limited by poor powder flow and compressibility. This study reported the development of a co-processed excipient comprising 98% mannitol and 2% pregelatinized rice starch (PRS) using spray drying with ammonium bicarbonate as a pore-forming agent. Methods: This optimized excipient demonstrated balanced powder flow and enhanced compressibility suitable for direct compression applications. The SeDeM expert system guided the optimization process by evaluating raw and spray-dried components. PRS exhibited excellent flowability that decreased after spray drying but displayed significantly enhanced compressibility, whereas mannitol maintained superior flow but continued to show limited compressibility post-drying. Scanning electron microscopy, differential scanning calorimetry, Fourier-transform infrared spectroscopy, and X-ray powder diffraction confirmed the absence of chemical interactions and unchanged wettability during co-processing. Results: The resulting excipient combined the favorable flow characteristics of mannitol with the improved compressibility of PRS, rendering it suitable for direct compression. Cetirizine dihydrochloride (CET) tablets were formulated via exponential curve fitting within the SeDeM framework, yielding an optimal CET-to-excipient ratio of 13:87. The tablets met all pharmacopeial physicochemical requirements, including uniform mass, adequate tensile strength, rapid disintegration, and dissolution profiles comparable to a reference product, with dissimilarity (f₁ = 4.28) and similarity (f₂ = 64.03) factors within regulatory acceptance limits. Conclusions: These findings represented the first application of SeDeM methodology to a co-processed mannitol–pregelatinized rice starch system, enabling predictive optimization of powder flow and compressibility in direct compression formulations. Full article

Background: Pulmonary administration offers a promising route for certain biologics, particularly when treating respiratory diseases. Spray drying is widely employed to produce inhalable powders with the biologics incorporated in a stabilizing amorphous sugar. Hydrophobic amino acids such as leucine are frequently added to improve dispersibility. Objectives: While the aerodynamic benefits of leucine are well established, its influence on irreversible moisture-induced dry powder particle aggregation and protein stability during storage remains less evaluated. Methods: In this work, inulin-based powders with and without 4 wt-% leucine were spray dried and stored at 43%, 58%, 69%, and 75% relative humidity (RH) at 20 ± 2 °C. Results: Immediately after drying, both formulations displayed comparable physicochemical characteristics. However, during storage of inulin-only formulations, dry powder particles showed viscous flow and formed big irreversible aggregates after storage at an RH of 58% and above, whereas leucine-containing powders remained intact across all tested conditions up to 20 days. Protein stability was assessed using lactate dehydrogenase (LDH) and β-galactosidase (β-gal) as model proteins. At 43% RH, the Tg remained above the storage temperature, and both LDH and β-gal retained their enzymatic activity for up to 20 days. At 75% RH, however, the Tg dropped to below storage temperature, resulting in a loss of stability for LDH, consistent with its reliance on vitrification. In contrast, β-gal maintained its activity at 75% RH, indicative of stabilization through water replacement. Conclusions: Overall, these results demonstrate that leucine enhances the physical stability of inulin powders by preventing irreversible aggregation under humid conditions. However, this effect does not extend to protecting proteins reliant on vitrification. These findings highlight the potential of inulin and leucine to reduce the need for stringent storage conditions of biologics. Full article