Formulation and In Vitro and In Silico Characterization of “Nano-in-Micro” Dry Powder Inhalers Containing Meloxicam

Abstract

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.

Pulmonary Delivery of Anticancer Drugs via Lipid-Based Nanocarriers for the Treatment of Lung Cancer: An Update

“…Furthermore, the dry powders have higher long-term stability, suitable for the formulation of lipophilic drugs [ 71 ]. Besides, DPIs can be produced as disposable devices, consequently limiting the contamination of the device and the environment [ 72 ]. Recently, many preclinical studies were published, including the development of inhaled anticancer drugs using DPIs for the treatment of LC, which reflects the growing interest in this approach [ 73 , 74 , 75 ].…”

Dry Powder Comprised of Isoniazid-Loaded Nanoparticles of Hyaluronic Acid in Conjugation with Mannose-Anchored Chitosan for Macrophage-Targeted Pulmonary Administration in Tuberculosis

“…Usually, the GSD values > 1.2 present the heterodispersive nature of the aerosols with broad particle size distribution [ 49 ]. The aerodynamic profile can further be improved by using the alternate drying procedure for the nanosuspensions to acquire the powder for inhalation, which has also been demonstrated by us in the past [ 50 ].…”

Preparation and Characterization of Ibuprofen Containing Nano-Embedded-Microparticles for Pulmonary Delivery

“…Spray-drying is a popular process from an industrial perspective because it is also cost and time efficient and scalable [ 33 , 34 , 35 , 36 ]. Preparation of nanosuspensions by sonication, combining nano spray-drying to produce dry powders, is suggested as a formulation approach for “nano-in-micro” particles with enhanced dissolution and aerosolization efficiency [ 37 , 38 , 39 , 40 , 41 ]. The novelty of this work was to formulate suitable nano-embedded-microparticles containing IBU for pulmonary delivery, using modern preparation techniques.…”