Recent developments in lactose blend formulations for carrier-based dry powder inhalation.

Pulmonary drug delivery can have several advantages over other administration routes, in particular when using dry powder formulations. Such dry powder inhalation formulations generally include natural and bio-inspired excipients, which, among other purposes, are used to improve dosing reproducibility and aerosolization performance. Amino acids can enhance powder dispersibility and provide protection against moisture uptake. Sugars are used as drug-carrying diluents, stabilizers for biopharmaceuticals, and surface enrichers. Lipids and lipid-like excipients can reduce interparticle adhesive forces and are also used as constituents of liposomal drug delivery systems. Finally, biodegradable polymers are used to facilitate sustained release and targeted drug delivery. Despite their promise, pulmonary toxicity of many of the discussed excipients remains largely unknown and requires attention in future research.

Natural and bioinspired excipients for dry powder inhalation formulations

Drug therapies for acute lung injury (ALI) are far from satisfactory, primarily because drugs cannot specifically target the lungs. Direct delivery of drugs to the deep alveolar regions by inhalation administration is crucial for the treatment of ALI. However, conventional inhalable carriers such as lactose and mannitol are generally inactive. Therefore, the use of a novel pharmacologically active carrier for pulmonary delivery may produce synergetic effects in treating ALI. Considering the pathophysiological environment of ALI, which typically featured excessive reactive oxygen species (ROS) and acute inflammation, we synthesized a novel kind of biodegradable and ROS-sensitive cross-linked covalent cyclodextrin frameworks (OC-COF) with uniform inhalable particle size to treat ALI. OC-COF was devised to incorporate H2O2-scavenging peroxalate ester linkages, which could hydrolyze and eliminate ROS generated in inflammatory sites. Ligustrazine (LIG), an antioxidant and anti-inflammatory natural compound, was loaded into OC-COF and evaluated as a dry powder inhaler (LIG@OC-COF) in vitro and in vivo, showing favorable aerodynamic properties and prominent antioxidant and anti-inflammatory capacities for the synergistic effects of OC-COF and LIG. In ALI rats, inhalation of LIG@OC-COF with a one-fifth LIG dose significantly alleviated the inflammation, oxidant stress, and lung damage. Western blot analysis demonstrated that LIG@OC-COF protected the lungs by regulating the Nrf2/NF-κB signaling pathway. In summary, this study provides a novel ROS-responsive material as an inhalable particulate carrier for the improved treatment of ALI and other medical conditions.

Antioxidant Biodegradable Covalent Cyclodextrin Frameworks as Particulate Carriers for Inhalation Therapy against Acute Lung Injury.

Characterization of excipient enhanced growth (EEG) tobramycin dry powder aerosol formulations.

High-shear mixer coatings as well as mechanofusion processes are used in the particle-engineering of dry powder inhalation carrier systems. The aim of coating the carrier particle is usually to decrease carrier–drug adhesion. This study comprises the in-depth comparison of two established dry particle coating options. Both processes were conducted with and without a model additive (magnesium stearate). In doing so, changes in the behaviour of the processed particles can be traced back to either the process or the additive. It can be stated that the coarse model carrier showed no significant changes when processed without additives. By coating the particles with magnesium stearate, the surface energy decreased significantly. This leads to a significant enhancement of the aerodynamic performance of the respective carrier-based blends. Comparing the engineered carriers with each other, the high-shear mixer coating shows significant benefits, namely, lower drug–carrier adhesion and the higher efficiency of the coating process.

In-Depth Comparison of Dry Particle Coating Processes Used in DPI Particle Engineering.

Performance tuning of particle engineered mannitol in dry powder inhalation formulations.

Particle engineered mannitol for carrier-based inhalation - A serious alternative?

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Performance tuning of particle engineered mannitol in dry powder inhalation formulations.

Particle engineered mannitol for carrier-based inhalation - A serious alternative?