Pulmonary delivery has high bioavailability, a large surface area for absorption, and limited drug degradation. Particle engineering is important to develop inhalable formulations to improve the therapeutic effect. In our work, the poorly water-soluble meloxicam (MX) was used as an active ingredient, which could be useful for the treatment of non-small cell lung cancer, cystic fibrosis, and chronic obstructive pulmonary disease. We aimed to produce inhalable “nano-in-micro” dry powder inhalers (DPIs) containing MX and additives (poly-vinyl-alcohol, leucine). We targeted the respiratory zone with the microcomposites and reached a higher drug concentration with the nanonized active ingredient. We did the following investigations: particle size analysis, morphology, density, interparticular interactions, crystallinity, in vitro dissolution, in vitro permeability, in vitro aerodynamics (Andersen cascade impactor), and in silico aerodynamics (stochastic lung model). We worked out a preparation method by combining wet milling and spray-drying. We produced spherical, 3–4 µm sized particles built up by MX nanoparticles. The increased surface area and amorphization improved the dissolution and diffusion of the MX. The formulations showed appropriate aerodynamical properties: 1.5–2.4 µm MMAD and 72–76% fine particle fraction (FPF) values. The in silico measurements proved the deposition in the deeper airways. The samples were suitable for the treatment of local lung diseases.

A fatal hereditary condition, cystic fibrosis (CF) causes severe lung problems. Ibuprofen (IBU), a non-steroidal anti-inflammatory drug, slows the progression of disease without causing significant side effects. Considering the poor water-solubility of the drug, IBU nanoparticles are beneficial for local pulmonary administration. We aimed to formulate a carrier-free dry powder inhaler containing nanosized IBU. We combined high-performance ultra-sonication and nano spray-drying. IBU was dissolved in ethyl acetate; after that, it was sonicated into a polyvinyl alcohol solution, where it precipitated as nanoparticles. Mannitol and leucine were added when producing dry particles using nano-spray drying. The following investigations were implemented: dynamic light scattering, laser diffraction, surface tension measurement, scanning electron microscopy, X-ray powder diffraction, differential scanning calorimetry, Fourier-transform infrared spectroscopy, in vitro dissolution test, and in vitro aerodynamic assessment (Andersen Cascade Impactor). The particle diameter of the IBU was in the nano range. The spray-dried particles showed a spherical morphology. The drug release was rapid in artificial lung media. The products represented large fine particle fractions and proper aerodynamic diameters. We successfully created an inhalable powder, containing nano-sized IBU. Along with the exceptional aerodynamic performance, the ideal particle size, shape, and drug-release profile might offer a ground-breaking local therapy for CF.

Pulmonary drug transport has numerous benefits. Large surface areas for absorption and limited drug degradation of the gastrointestinal system are provided through the respiratory tract. The administration is painless and easy for the patient. Due to their better stability when compared to liquid formulations, powders have gained popularity among pulmonary formulations. In the pharmaceutical sector, quality assurance and product stability have drawn a lot of attention. Due to this, it was decided to perform a long-term stability study on a previously developed, nanosized dry powder inhaler (DPI) formulation that contained meloxicam. Wet milling was implemented to reduce the particle size, and nano spray-drying was used to produce the extra-fine inhalable particles. The particle diameter was determined using dynamic light scattering and laser diffraction. Scanning electron microscopy was utilized to describe the morphology. X-ray powder diffraction and differential scanning calorimetry were applied to determine the crystallinity. In an artificial lung medium, the in vitro dissolution was studied. The Andersen Cascade Impactor was used to investigate the in vitro aerodynamic characteristics. The stability test results demonstrated that the DPI formulation maintained its essential qualities after 6 and 12 months of storage. Consequently, the product might be promising for further studies and development.

Background/Objectives: Research on cyclodextrin-based metal-organic frameworks (CD-MOFs) is still in its infancy, but their potential for use in drug delivery—expressly in the lung—seems promising. We aimed to use the freeze-drying method to create a novel approach for preparing CD-MOFs. MOFs consisting of γ-cyclodextrin (γCD) and potassium cations (K⁺) were employed to encapsulate the poorly water-soluble model drug Ibuprofen (IBU) for the treatment of cystic fibrosis (CF). Methods: Using the LeanQbD^® software (v2022), we designed the experiments based on the Quality by Design (QbD) concept. According to QbD, we identified the three most critical factors, which were the molar ratio of the IBU to the γCD, incubation time, and the percentage of the organic solvent. light-, scanning electron microscope (SEM) and laser diffraction were utilized to observe the morphology and particle size of the samples. In addition, the products were characterized by Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRPD), Fourier Transform Infrared Spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). Results: Based on characterizations, we concluded that a γCD-MOF/IBU complex was also formed using the freeze-drying method. Using formulations with optimal aerodynamic properties, we achieved 38.10 ± 5.06 and 47.18 ± 4.18 Fine Particle Fraction% (FPF%) based on the Andersen Cascade Impactor measurement. With these formulations, we achieved a fast dissolution profile and increased IBU solubility. Conclusions: This research successfully demonstrates the innovative use of freeze-drying to produce γCD-MOFs for inhalable IBU delivery. The method enabled to modify the particle size, which was crucial for successful pulmonary intake, emphasizing the need for further investigation of these formulations as effective delivery systems.

Background/Objectives: Dry powder inhalation is an attractive research area for development. Therefore, this work aimed to develop inhalable co-spray-dried theophylline (TN) microparticles, utilizing raffinose-amino acid fine carriers intended for asthma therapy. The study addressed enhancing TN’s physicochemical and aerodynamic properties to ensure efficient lung deposition. Methods: The process involves spray-drying each formulation’s solution using a mini spray drier. A rigorous assessment was conducted on particle size distribution, structural and thermal analysis, morphology study, in vitro and in silico aerodynamic investigation, and aerodynamic particle counter in addition to the solubility, in vitro dissolution, and diffusion of TN. Results: The carriers containing leucine and glycine revealed superior characteristics (mass median aerodynamic diameter (MMAD): 4.6–5 µm, fine particle fraction (FPF): 30.6–35.1%, and amorphous spherical structure) as candidates for further development of TN-DPIs, while arginine was excluded due to intensive aggregation and hygroscopicity, which led to poor aerodynamic performance. TN co-spray-dried samples demonstrated fine micronized particles (D [0.5]: 3.99–5.96 µm) with predominantly amorphous structure (crystallinity index: 24.1–45.2%) and significant solubility enhancement (~19-fold). Formulations containing leucine and leucine-glycine revealed the highest FPF (45.7–47.8%) and in silico lung deposition (39.3–40.1%), rapid in vitro drug release (~100% within 10 min), and improved in vitro diffusion (2.29–2.43-fold), respectively. Moreover, the aerodynamic counter confirmed the development of fine microparticles (mean number particle size = 2.3–2.02 µm). Conclusions: This innovative formulation possesses enhanced physicochemical, morphological, and aerodynamic characteristics of low-dose TN for local asthma treatment and could be applied as a promising carrier for dry powder inhaler development.

Background: Cystic fibrosis is a hereditary disease, which causes the accumulation of dense mucus in the lungs accompanied by frequent local inflammation. The non-steroidal anti-inflammatory drug ibuprofen (IBU) and the mucolytic mannitol (MAN) can treat these symptoms. Compared to per os administration, a lower dose of these drugs is sufficient to achieve the desired effect by delivering them in a pulmonary manner. However, it is still a challenge to administer high drug doses to the lungs. We aim to develop two inhaled powder formulations, a single-drug product of MAN and a combined formulation containing IBU and MAN. Methods: MAN was dissolved in an aqueous solution of Poloxamer-188 (POL). In the case of the combined formulation, a suspension was first prepared in a planetary mill via wet milling in POL medium. After the addition of leucine (LEU), the formulations were spray-dried. The prepared DPI samples were analyzed by using laser diffraction, scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, density tests, in vitro aerodynamic studies (Andersen Cascade Impactor, Spraytec^® device), in vitro dissolution tests in artificial lung fluid, and in silico tests with stochastic lung model. Results: The DPIs showed suitability for inhalation with low-density spherical particles of appropriate size. The LEU-containing systems were characterized by high lung deposition and adequate aerodynamic diameter. The amorphization during the procedures resulted in rapid drug release. Conclusions: We have successfully produced a single-drug formulation and an innovative combination formulation, which could provide complex treatment for patients with cystic fibrosis to improve their quality of life.