Spray-dried Powders Research Articles

An experimental study of the effect of individual upper airway anatomical features on the deposition of dry powder inhaler formulations

This study aims to investigate the effects of different pharynx anatomical features on the delivery of inhaled aerosols. Six in-vitro upper airway models reconstructed using anatomical images acquired by Magnetic Resonance Imaging (MRI) were used for the experiments. A geometrically accurate airway model was produced, and five other different airway models, each missing one or more specific anatomical features: the uvula, epiglottis, and/or soft palate, were derived from the original model. Hence, the geometrical boundaries of the six models were the same except at regions where specific anatomical structures were removed, and this was done to allow meaningful comparisons between the different geometries to be made using specific measurements. Spray-dried mannitol powder (volume median particle size and span were 3.22 μm and 1.90 μm, respectively) was loaded into a capsule-based dry powder inhaler with different resistance, an Osmohaler™ (low resistance), or Handihaler® (high resistance), attached to the inlet of the airway model, which its outlet was connected to a Next-Generation Impactor (NGI). The studies were performed using flow rates of 30 and 60 LPM. High-performance liquid chromatography (HPLC) was used to quantify the mass deposition of particles in different stages of the NGI and airway replicas. Results from this study show that widening the space between the oral cavity and oropharynx, exemplified by one of the six replicas developed, significantly decreases upper airway deposition as well as increases the fine particle fraction. The case with the highest deposition (63.5%) occurred in the pharynx replica with the soft palate present (at 60 LPM with the Hanihaler), while the lowest deposition (26.0%) occurred in the replica without the soft palate and epiglottis (at 30 LPM with the Osmohaler). This study highlights that in addition to the resistance of the inhalers, their interactions with the human airway anatomical features are likely to play important roles in the subsequent lung dose. Results from this study are novel because while the effects of different inhaler resistance in a given airway replica is known, the effects contributed by specific pharynx anatomical features on particle transport behaviour have not been studied experimentally or reported on in the literature. This study shows that space adjacent to the soft palate affects particle deposition dramatically but the effect appears to be more significant when using the Handihaler and for the high flow rate cases.

In Vitro and In Vivo Performance of Pickering Emulsion-Based Powders of Omega-3 Polyunsaturated Fatty Acids.

Omega-3 polyunsaturated fatty acids (n-3 PUFA) are essential nutrients for human health and have been linked to a variety of health benefits, including reducing the risk of cardiovascular diseases. In this paper, a spray-dried powder formulation based on Pickering emulsions stabilized with cellulose nanocrystals (CNC) and hydroxypropyl methylcellulose (HPMC) has been developed. The formulation was compared in vitro and in vivo to reference emulsions (conventional Self-Emulsifying Drug Delivery System, SEDDS) to formulate n-3 PUFA pharmaceutical products, specifically in free fatty acid form. The results of in vivo studies performed in fasted dogs showed that Pickering emulsions reconstituted from powders are freely available (fast absorption) with a similar level of bioavailability as reference emulsions. In the studies performed with dogs in the fed state, the higher bioavailability combined with slower absorption observed for the Pickering emulsion, compared to the reference, was proposed to be the result of the protection of the n-3 PUFAs (in free fatty acid form) against oxidation in the stomach by the solid particles stabilizing the emulsion. This observation was supported by promising results from short-term studies of chemical stability of powders with n-3 PUFA loads as high as 0.8 g oil/g powder that easily regain the original emulsion drop sizes upon reconstitution. The present work has shown that Pickering emulsions may offer a promising strategy for improving the bioavailability and stability as well as providing an opportunity to produce environmentally friendly (surfactant free) and patient-acceptable solid oral dosage forms of n-3 PUFA in the free fatty acid form.

Optimization of Highly Porous Mannitol Preparation using Ammonium bicarbonate and Citric acid as Templating Agents with Spray Drying Technique

This study investigated the effect of ammonium bicarbonate and citric acid as templating agents using spray drying technique to improve the porosity of D-mannitol powder. It has been shown that textural properties, such as surface area and pore volume produced, are affected by the type and concentration of templating agents, inlet temperature, and outlet temperature of spray drying. The structure of mannitol powder produced changes considerably due to the change in its textural properties to particle powder with high porosity, surface area, and pore volume. The results show that the ratio of D-mannitol to ammonium bicarbonate 10:5 w/w% with water solvent temperature of 30 oC, spray drying inlet temperature of 120 oC, and spray drying outlet temperature of 70 oC, resulting in the highest porosity, surface area, and pore volume. The surface area of mannitol increased from 1.167 m2/g to 3.571 m2/g, followed by an increase in pore volume from 0.0022 cc/g to 0.012 cc/g and pore diameter from 75.33 Å to 115.2 Å. The scanning electron microscope (SEM) results are consistent with the surface area measurement results using the Surface Area Analyzer (SAA). The resulting spray-dried mannitol powder with a high specific surface area allows it to be used as an excipient in solid formulations of oral preparations.

Comparison of live microalgae and Spray-dried algae powder effects on growth, digestive and antioxidant capacity of juvenile pearl oyster Pinctada maxima

The pearl production through the pearl oyster Pinctada maxima’s culture has developed slowly over the past decades due to over-fishing of wild populations and mass mortality at juvenile stages. Indoor farming is an alternative mode for P. maxima juvenile cultivation to improve survival rates. In pursuit of optimizing healthy management under the indoor farming mode, the objective of this investigation was to compare the growth performance, digestion, and antioxidant capacity of juveniles fed with different microalgae-based diets (live Isochrysis zhanjiangensis, Platymonas subcordiformis, Chaetoceros muelleri; and spray-dried I. zhanjiangensis, P. subcordiformis, C. muelleri powder). The juvenile survival rates fed with spray-dried microalgae powder (except C. muelleri powder) were not significantly different from those fed on live microalgae. However, the growth performance of juveniles fed with spray-dried microalgae powder could have been better than the live one. The digestive enzymatic activities were consistent with growth performance, and diets affected the antioxidant capacity. The spray-dried I. zhanjiangensis powder can serve as a substitute for live microalga in P. maxima juvenile indoor farming and is recommended under controlled conditions. The findings from this study would provide essential data to improve health management for P. maxima juveniles in indoor farming conditions.

Understanding the impact of mannitol on physical stability and aerosolization of spray-dried protein powders for inhalation

Pulmonary delivery of protein-based therapeutics, including antibodies, is a promising option for treating respiratory diseases. Spray drying is a widely used method for producing dry powder formulations with mannitol being a commonly used excipient for these inhalation formulations. There is limited research available concerning the utilization of mannitol as an excipient in the spray drying of proteins and its impact on aerosol performance. This study highlights the importance to understand mannitol’s potential role and impact in this context. To investigate the impact of mannitol on physical stability and aerosolization of spray-dried protein formulations, bovine serum albumin (BSA) was employed as a model protein and formulated with different concentrations of mannitol via spray drying. The spray-dried solids were characterized for their particle size using Malvern mastersizer and aerodynamic particle size using next generation impactor (NGI). Additionally, the solids were characterized with solid-state Fourier-transform infrared spectroscopy (ssFTIR), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) and solid-state nuclear magnetic resonance spectroscopy (ssNMR) to analyze the change in their secondary structure, crystallinity, particle morphology, and protein-excipient interaction, respectively. Size exclusion chromatography (SEC) was used to investigate changes in monomer content resulting from storage under stressed condition of 40 °C. Protein formulations containing more than 33 % mannitol by weight showed crystallization tendencies, causing an increase in monomer loss over time. ssNMR data also showed mixing heterogeneity of BSA and mannitol in the formulations with high mannitol contents. Futhermore, fine particle fraction (FPF) was found to decrease over time for the formulations containing BSA: Mannitol in the ratios of 2:1, 1:2, and 1:5, due to particle agglomeration induced by crystallization of mannitol. This study underscores the significant influence of excipients such as mannitol on the aerosol performance and storage stability of spray-dried protein formulations.

Storage stability and anti-caking agents in spray-dried fruit powders: A review

Fruit powders possess numerous benefits compared to fresh raw materials, i.e., extended shelf-life, convenient transportation and storage, a wide range of applications, etc. Nonetheless, the storage time of fruit powders depends on such factors as storage conditions, packaging, etc.
 This review suggests a comprehensive analysis of articles, reviews, reports, and books indexed in Scopus, Web of Science, and eLIBRARY.RU, as well as reported at conference proceedings and other scholarly resources in 2005–2022.
 Due to their high hygroscopicity, powders tend to absorb moisture from the environment and become prone to caking. Anticaking agents can prevent powders from this process. Different packaging materials also affect the compounds and properties of fruit powders. Accelerated degradation and temperature models can predict shelfp-life. This review featured the effectiveness of different anti-caking agents, as well as the impact of various packaging methods on the storage of powders. Calcium phosphate demonstrated excellent anti-caking properties, reduced hygroscopicity, and enhanced flowability. Aluminum laminated packaging proved effective in protecting powders during storage. As the storage time increased, powders demonstrated only a slight increase in moisture content. Their L* value (light to dark) and b* value (yellow to blue) decreased while the a* value (green to red) and the total color change increased. Caking increased as the flowability, pigment content, and antioxidant content went down.
 The review has practical implications for developing new technologies aimed at prolonging the storage time of spray-dried fruit powders.

The Development of Oral Solid Dosage Forms Using the Direct-Compression Tableting of Spray-Dried Bacteriophages Suitable for Targeted Delivery and Controlled Release

This study addresses the challenge of developing a cheap, patient-friendly alternative to antibiotics using bacteriophages for gastrointestinal applications. It explores the feasibility of manufacturing an enteric solid dosage form containing a salmonella-specific Myoviridae phage, Felix O1, encapsulated in spray-dried trehalose/Eudragit microparticles. The spray-dried powder was further formulated by combining the spray-dried microparticles with magnesium stearate to facilitate the fabrication of tablets using direct compression. The paper presents a comprehensive evaluation of the tablets with measurements of phage viability during tablet fabrication using a range of compression settings and, after tablet disintegration, dissolution and friability. Phage viability measurements were performed using storage stability testing of spray-dried powders and tablets in sealed vials at 4 °C, 20 °C and 30 °C and under different humidity conditions of 0%, 50% and 65% RH. The recommended compression force range was found to be 10–15 kN for a standard 10 mm diameter tablet. The storage of tablets at 4 °C/0% RH was found to be the most favourable condition resulting in a ~1 log loss in titre over a six-month storage period. Storage at higher temperatures and samples exposed to high levels of humidity resulted in a significant loss in phage viability. The paper highlights challenges in developing phage formulations suitable for direct-compression tableting, which afford the phages protection when exposed to temperatures and humidity levels that do not require a cold supply chain.

Microencapsulation of micronized tart cherry puree: Characterization and physicochemical assessment

Tart cherries are known for their high phenolic content and a plethora of health benefits pertaining to heart health, muscle recovery, sleep quality, inflammation, and arthritis, to name a few. However, maximizing the bioavailability of these bioactive food components is often a challenge in the food and beverage industry. The aim of this research was to investigate the spray drying process for microencapsulation to increase the stability of compounds and improve their release properties, thereby resulting in enhanced bioavailability. In our study, we investigated the effects of micronization methods and microencapsulation using wall material combinations on the physical attributes, morphology, and chemical properties of spray-dried tart cherry microcapsules. Micronized and non-micronized purée was spray-dried utilizing different ratios of maltodextrin (MD) and gum arabic (GA) as wall materials. The microcapsules were evaluated for process yield, color, hygroscopicity, particle surface shape using Scanning Electron Microscopy (SEM), anthocyanin encapsulation efficiency, antioxidants and phenolics. The results demonstrated that the total phenolics, flavonoid content, and antioxidant activity increased for all wall material conditions with a reduction in particle size. The findings suggest that high-pressure homogenization (HPH) and the combination of MD and GA in an equal ratio (MD: GA 15%:15%) can effectively improve the extractability of phenolics and antioxidants. This study underscores the potential of spray-dried fruit juice powders and contributes to filling the current knowledge gap regarding the microencapsulation of tart cherries, particularly in the context of micronized fruit purées.

QbD assisted development of inhalable spray-dried erlotinib procubosomal system for the effective management of non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the most common and leading cause of cancer deaths worldwide. Erlotinib (ERL), an epidermal growth factor receptor (EGFR) kinase inhibitor, has been used as a primary prescription for the effective treatment of metastatic NSCLC. However, it has poor aqueous solubility, extensive first-pass metabolism, oral administration-related toxicities, and inconveniences for cancer patients with gastrointestinal tract (GIT) disorders that limit its therapeutic potential. To resolve the above challenges, inhalable ERL-loaded spray-dried procubosomal powder (ERL-SDPP) was developed employing a Box-Behnken design that exhibit impressive characteristics including a device removal efficiency (DRE) of 84.7 ± 2.37 %, aerosolization efficiency (AE) of 18.1 ± 0.75, fine particle fraction (FPFTSI) of 33.7 ± 1.28 %, drug content (DC) of 93.6 ± 3.9 %, and a reconstituted cubosome size (PS) of 453.87 ± 14.65 nm. During in-vitro characterization, the optimized inhalable ERL-SDPP formulation was found to have 96.2 ± 3.98 % entrapment efficiency, −28.6 ± 1.38 mV zeta potential, and 3.29 ± 0.53 μm mass median aerodynamic diameter (MMAD). In-vitro drug release studies revealed sustained release behavior of ERL from ERL-SDPP lasting up to 36 h, demonstrating the increased dissolution profile and stability of ERL-SDPP in simulated lung fluids compared to pure ERL. In-vitro cytotoxicity studies utilizing A549 cell lines uncovered the greater potential of ERL-SDPP formulation, with a ∼1.5-fold reduction in IC50 compared to pure ERL, after 24 h treatment. In-vivo pharmacokinetic parameters revealed that inhalable ERL-SDPP exhibited a 1.76-fold and 6.25-fold higher AUC than oral and intravenous administered ERL, respectively. Organ distribution studies confirmed enhanced retention and accumulation of ERL in lungs after administration of inhalable ERL-SDPP compared to oral ERL, thereby reducing the dose and related systemic toxicities. Thus, the developed inhalable ERL-SDPP has shown promise to improve therapeutic potential against NSCLC through a site-specific sustained drug delivery system as it requires lower doses and limits systemic side effects.

Supersaturable Solid Self-microemulsifying Delivery Systems of Astaxanthin via Spray Drying: Effects of Polymers and Solid Carriers.

This study aimed to develop the solid astaxanthin-encapsulated self-microemulsifying delivery system (S-AST SMEDS) spray-dried particles and investigate the effect of materials in formulations on product characteristics. The optimized liquid AST SMEDS incorporated with a polymeric precipitation inhibitor (PI) was solidified with a solid carrier by spray drying. Physicochemical properties of S-AST SMEDS spray-dried powders including morphology, particle size and distribution, flowability, solid-state characters, moisture content, yield, loading capacity of AST, and reconstitution properties were examined. Polymeric PIs seemed to have an impact on particles' size, surface smoothness, and flowability while solid carriers had an effect on the particles' moisture content and droplet size of microemulsions obtained after reconstitution. The amount of AST encapsulated in S-SMEDS powder was influenced by both polymer and solid carriers. Dissolution and short-term stability of S-AST SMEDS were also studied. Our developed spray-dried solid SMEDS particles helped enhance AST dissolution rate.

The biocontrol agent Lactiplantibacillus plantarum AMBP214 is dispersible to plants via bumblebees.

Plant protection products are essential for ensuring food production, but their use poses a threat to human and environmental health, and their efficacy is decreasing due to the acquisition of resistance by pathogens. Stricter regulations and consumer demand for cleaner produce are driving the search for safer and more sustainable alternatives. Microbial biocontrol agents, such as microorganisms with antifungal activity, have emerged as a promising alternative management strategy, but their commercial use has been limited by poor establishment and spread on crops. This study presents a novel system to overcome these challenges. The biocontrol agent Lactiplantibacillus plantarum AMBP214 was spray-dried and successfully dispersed to strawberry flowers via bumblebees. This is the first report of combining spray-dried, non-spore-forming bacteria with pollinator-dispersal, which scored better than the state-of-the-art in terms of dispersal to the plant (CFU/flower), and resuscitation of the biocontrol agent. Therefore, this new entomovectoring system holds great promise for the use of biocontrol agents for disease management in agriculture.

Effect of coating material on microencapsulated phenolic compounds extracted from agroindustrial ciriguela peel residue.

Extract of ciriguela residue was microencapsulated by spray-drying and freeze-drying using maltodextrin (M), gum arabic (GA) and their mixture (50% M; 50% GA on dry basis) as encapsulating agents. Total phenolic compounds (TPC), antioxidant activity, physicochemical properties, profile of phenolic compounds by HPLC with diode-array detection and storage stability were evaluated. TPC content of powders ranged from 306.9 to 451.2 mg gallic acid equivalent g-1 dry powder. The spray-dried powder prepared using GA as encapsulating agent had higher TPC content and antioxidant activity, whereas the freeze-dried powder had lower moisture and water activity. Spray-dried microcapsules had spherical shape, whereas freeze-dried products had irregular structures. The profile of phenolic compounds identified in samples was similar, with rutin (342.59 and 72.92 μg g-1 ) and quercetin (181.02 and 43.24 μg g-1 ) being the major compounds in liquid and freeze-dried extracts, respectively, whereas myricetin (97.41 μg g-1 ) was predominant in spray-dried ones. Storage stability tests carried out for 45 days at 7 or 25 °C revealed no statistically significant difference in TPC. Ciriguela residue can be considered a source of TPC and used as ingredient with good antioxidant activity in the food industry. © 2023 Society of Chemical Industry.

Spray Drying Enzyme-Treated Cellulose Nanofibrils.

Enzyme-treated cellulose nanofibrils (CNFs) were produced via a lab-scale mass colloider using bleached kraft pulp (BKP) to evaluate their processability and power requirements during refining and spray-drying operations. To evaluate the energy efficiency in the CNF refining process, the net energy consumption, degree of polymerization (DP), and viscosity were determined. Less energy was consumed to attain a given fines level by using the endoglucanase enzymes. The DP and viscosity were also decreased using the enzymes. The morphological properties of the enzyme-pretreated spray-dried CNF powders (SDCNFs) were measured. Subsequently, the enzyme-pretreated SDCNFs were added to a PP matrix with MAPP as a coupling agent. The mixture was then compounded through a co-rotating twin-screw extruder to determine whether the enzyme treatment of the CNFs affects the mechanical properties of the composites. Compared to earlier studies on enhancing PMCs with SDCNF powders, this research investigates the use of enzyme-pretreated SDCNF powders. It was confirmed that the strength properties of PP increased by adding SDCNFs, and the strength properties were maintained after adding enzyme-pretreated SDCNFs.

Evaluation of Microgels Derived from Spray-Dried Aquafaba Powder for Improved Foam Quality

Evaluation of Microgels Derived from Spray-Dried Aquafaba Powder for Improved Foam Quality

Storage of spinach juice agglomerates: Physical, flow, structural, and thermal properties.

The objective of this study was to investigate how the various storage temperatures affected the physical properties, flow characteristics, microstructure, and glass transition temperature of spinach juice agglomerates. For this purpose, spray-dried spinach juice powders were processed to agglomerates by using a modified fluidized bed dryer (1.6 m/s airflow rate, 60°C drying air temperature, 20 min processing time, and with different binder solutions containing agents as maltodextrin, gum Arabic, and whey powder isolate). The analyses were carried out every month throughout 6 months while the spinach juice agglomerates were stored at temperatures of 4, 20, and 35°C. The results revealed that over the storage time, the moisture content and water activity values of the agglomerates were generally under 11% and 0.6, respectively. The color values generally showed a decreasing trend depending on the storage time. The solubility times of the samples stored at 4°C were longer than those of stored at other storage temperatures. The SJA-GA had the lowest HR and CI values and thus the best flowability properties during all storage times. There was no detectable change in the structures of SJA stored at 20°C according to the storage time. Throughout the storage time, it was discovered that the glass transition temperature of all spinach juice agglomerates was remarkably similar. Overall, the investigation revealed that storage at 35°C for 6 months might be suitable because it delivered the intended outcomes such as greater flowability and cohesiveness, and shorter wettability and solubility times.

Moisture sorption isotherm and effective diffusion coefficient of porcelain stoneware spray-dried powder

Moisture sorption isotherm and effective diffusion coefficient of porcelain stoneware spray-dried powder

The effects of drying methods and leucine addition on properties of propolis powder: Towards the development of a new formulation

Propolis, a valuable resin from beehives has many potential health benefits. In this study, we examine the effects of addition of L-Leucine (LL) on the properties of propolis powder produced by spray and freeze drying. Gum Arabic (GA) with LL at different ratios were used as wall materials. Adding LL increases the yield of spray dried (SD) propolis powders, while hygroscopicity, flowability and reconstitution characteristics were affected by both drying method and LL concentration. Freeze dried (FD) powders were more porous as evident by the scanning electron micrographs and showed release of >90 % of compounds within 15 min in both gastric and intestinal media. SD powders were spherical and showed a sustained release of compounds in both media. The best powders were produced with a GA to LL ratio of 8:2 dried by spray drying at 120 °C or 150 °C and by freeze drying. These three optimized formulations showed greater yields (> 50 %), lower hygroscopicity (< 10 %) and moderate antioxidant and antibacterial activities. The formulations remained stable for up to 6 months at ambient temperature, but instability was observed at 40 °C. In conclusion, leucine addition facilitates the formation of SD and FD propolis powders with good properties.

Storage stability of a fluidized-bed agglomerated spray-dried strawberry powder mixture.

Background: Strawberry is a fruit with a high antioxidant capacity due to its richness in phenolic compounds that suffer a rapid post-harvest deterioration. Spray drying is an alternative to reduce losses; however, these powders present problems of instantanisation, making it necessary to implement agglomeration processes. During storage, powdered food products can undergo a series of changes in their amorphous state from a product initially in a vitreous state to a gummy state, where all properties are substantially modified due to the increased mobility of water in the matrix. Methods: The research objective was to evaluate the storage stability (6 months) of a fluidized bed agglomerated strawberry powder mixture at three temperatures (15, 25 and 25°C), a controlled environment at 65% relative moisture, and PET foil laminated film bags as packaging. Moisture, water activity, bulk and compacted density, Carr and Hausner indices, solubility, hygroscopicity, wettability, angle of repose, antioxidant capacities, total phenols, anthocyanins, vitamin C, color (CIE-Lab) and particle size were monitored. Results: ANOVA showed statistically significant differences (p<0.05) for all dependent variables concerning storage time; storage temperature had no significant effect on S, ABTS, DPPH and Hu. The time-temperature interaction during storage had no significant effect (p>0.05) on S, ABTS, DPPH, Hu and L. The agglomerate showed moisture and aw values that confer excellent stability against deterioration reactions; it retained good fluidity, low cohesiveness, and retentions above 50% for antioxidant capacity, 76% for total phenols, 39% for anthocyanins, and 40% for vitamin C; particle size was retained during the evaluation. The color was only affected in the 35°C treatment from the fifth month onwards. Conclusions: The study will serve as a tool for the determination of the shelf life of the chipboard once the critical values of the attributes selected as predictors of shelf life are defined.

Inhalable dry powder containing remdesivir and disulfiram: Preparation and in vitro characterization

The respiratory tract, as the first and most afflicted target of many viruses such as SARS-CoV-2, seems to be the logical choice for delivering antiviral agents against this and other respiratory viruses. A combination of remdesivir and disulfiram, targeting two different steps in the viral replication cycle, has showed synergistic activity against SARS-CoV-2 in-vitro. In this study, we have developed an inhalable dry powder containing a combination of remdesivir and disulfiram utilizing the spray-drying technique, with the final goal of delivering this drug combination to the respiratory tract. The prepared dry powders were spherical, and crystalline. The particle size was between 1 and 5 μm indicating their suitability for inhalation. The spray-dried combinational dry powder containing remdesivir and disulfiram (RDSD) showed a higher emitted dose (ED) of >88% than single dry powder of remdesivir (RSD) (∼72%) and disulfiram (DSD) (∼84%), with a fine particle fraction (FPF) of ∼55%. Addition of L-leucine to RDSD showed >60% FPF with a similar ED. The in vitro aerosolization was not significantly affected after the stability study conducted at different humidity conditions. Interestingly, the single (RSD and DSD) and combined (RDSD) spray-dried powders showed limited cellular toxicity (CC50 values from 39.4 to >100 µM), while maintaining their anti-SARS-CoV-2 in vitro (EC50 values from 4.43 to 6.63 µM). In a summary, a combinational dry powder formulation containing remdesivir and disulfiram suitable for inhalation was developed by spray-drying technique which showed high cell viability in the respiratory cell line (Calu-3 cells) retaining their anti-SARS-CoV-2 property. In the future, in vivo studies will test the ability of these formulations to inhibit SARS-CoV-2 which is essential for clinical translation.

In Vitro and In Vivo Evaluation of Inhalable Ciprofloxacin Sustained Release Formulations.

Respiratory antibiotics delivery has been appreciated for its high local concentration at the infection sites. Certain formulation strategies are required to improve pulmonary drug exposure and to achieve effective antimicrobial activity, especially for highly permeable antibiotics. This study aimed to investigate lung exposure to various inhalable ciprofloxacin (CIP) formulations with different drug release rates in a rat model. Four formulations were prepared, i.e., CIP-loaded PLGA micro-particles (CHPM), CIP microcrystalline dry powder (CMDP), CIP nanocrystalline dry powder (CNDP), and CIP spray-dried powder (CHDP), which served as a reference. The physicochemical properties, drug dissolution rate, and aerosolization performance of these powders were characterized in vitro. Pharmacokinetic profiles were evaluated in rats. All formulations were suitable for inhalation (mass median aerodynamic diameter < 5 µm). CIP in CHPM and CHDP was amorphous, whereas the drug in CMDP and CNDP remained predominantly crystalline. CHDP exhibited the fastest drug release rate, while CMDP and CNDP exhibited much slower drug release. In addition, CMDP and CNDP exhibited significantly higher in vivo lung exposure to CIP compared with CHDP and CHPM. This study suggests that lung exposure to inhaled drugs with high permeability is governed by drug release rate, implying that lung exposure of inhaled antibiotics could be improved by a sustained-release formulation strategy.