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Dry powder inhalers (DPIs) have gained increasing clinical acceptance in the local treatment of lung diseases due to their ability to meet the evolving needs of patients while avoiding environmental concerns. However, some formulations for DPIs still encounter performance limitations in terms of aerodynamic properties and achievement of therapeutic doses. Innovative aerogel powder formulations for DPIs processed using combined supercritical CO2 (scCO2)-based technologies can overcome these limitations, especially in the case of poorly water-soluble drugs. The loading of hydrophobic drugs into aerogels can be optimized through a thorough understanding of the physicochemical properties of the formulation and the scCO2 processing conditions. In this study, drug-loaded alginate aerogel particles were prepared by combining gelation-emulsification techniques and scCO2-based technologies. Beclomethasone dipropionate (BDP), a hydrophobic corticosteroid, was incorporated into the aerogel matrix by scCO2 impregnation. The influence of contact time, initial amount of drug, and use of co-solvents on the efficiency of scCO2 impregnation were studied. The kinetics of the BDP adsorption process was modelled to elucidate the time required for the drug to attain equilibrium concentration under specific operating conditions. Nitrogen adsorption-desorption and helium pycnometry revealed particles with large surface area (>200 m2/g) and porosity (ca. 90%). The resulting aerogels had excellent aerodynamic properties at relevant BDP doses, as confirmed by in vitro lung deposition tests. Ex vivo permeability tests with porcine lung tissues evidenced that BDP released from the inhaled formulation could penetrate the bronchial tissue

Inkjet printing is as an emerging technique in the biomedical field offering cost-effective solutions for flexible production and the engineering of personalized medicine solutions. Thermal inkjet printing technology in the “drop-on-demand” mode allows the design of fully automated deposition patterns with high spatial resolution for applications ranging from microparticles in drug formulations to cell deposition in regenerative medicine. In particular, novel formulations in the form of porous particles are sought for the treatment of respiratory disorders and the systemic administration of bioactive compounds using the pulmonary route. Aerogel particles, i.e. highly porous and light-weight nanoporous powders, are particularly promising as carriers for the pulmonary route. In this work, the preparation of aerogel microspheres by thermal inkjet printing followed by supercritical drying is presented for the first time to overcome the current processing limitations. Alginate aerogel particles were loaded with salbutamol sulphate, a bronchodilator used for the treatment of asthma attacks and chronic obstructive pulmonary disease, as a model drug for sustained pulmonary delivery. The optimized processing method allowed the preparation of reproducible nanostructured microparticles with modified salbutamol sulphate release profile and aerodynamic performance of relevance for oral inhalation purposes

Physico-chemical properties of lactose are key factors in adhesive mixtures used as dry powder inhaler (DPI). Despite the abundant literature on this topic, the effect of the polymorphism and pseudo-polymorphism of lactose has been seldom investigated and discussed although often lactose used in DPI is subjected to unit operations, which may alter its solid-state properties. Here, we studied the aerosolization performance of salbutamol sulphate (SS) or budesonide (BUD) formulations by investigating the effect of lactose pseudopolymorphism in ternary (coarse lactose/fine lactose/drug) and binary (coarse lactose/drug) mixtures. An improvement of the aerosolization performance of SS formulations with the increase of the amount of fine micronized lactose up to 30% (fine particle fraction (FPF) = 57%) was observed. Micronized lactose contained hygroscopic anhydrous α-lactose, which converted to α-lactose monohydrate at ambient conditions. This implied that the positive effect of fines on the aerosolization performance decreased and eventually disappeared with the formulation aging. Positive effect on SS deposition was observed also with binary mixtures with anhydrous lactose, whereas the opposite occurred with budesonide-containing formulations. The collected data demonstrated the crucial role of the carrier crystal form on the positive effect of fines on the deposition.