Targeting of Inhaled Therapeutics to the Small Airways: Nanoleucine Carrier Formulations

Current dry powder formulations for inhalation deposit a large fraction of their emitted dose in the upper respiratory tract where they contribute to off-target adverse effects and variability in lung delivery. The purpose of the current study is to design a new formulation concept that more effectively targets inhaled dry powders to the large and small airways. The formulations are based on adhesive mixtures of drug nanoparticles and nanoleucine carrier particles prepared by spray drying of a co-suspension of leucine and drug particles from a nonsolvent. The physicochemical and aerosol properties of the resulting formulations are presented. The formulations achieve 93% lung delivery in the Alberta Idealized Throat model that is independent of inspiratory flow rate and relative humidity. Largely eliminating URT deposition with a particle size larger than solution pMDIs is expected to improve delivery to the large and small airways, while minimizing alveolar deposition and particle exhalation.

Targeting of Inhaled Therapeutics to the Small Airways: Nanoleucine Carrier Formulations

Current dry powder formulations for inhalation deposit a large fraction of their emitted dose in the upper respiratory tract where they contribute to off-target adverse effects and variability in lung delivery. The purpose of current study is to design a new formulation concept that more effectively targets inhaled dry powders to the large and small airways. The formulations are based on adhesive mixtures of drug nanoparticles and nanoleucine carrier particles prepared by spray drying of a co-suspension of leucine and drug particles from a nonsolvent. The physicochemical and aerosol properties of the resulting formulations are presented. The formulations achieve 93% lung delivery in the Alberta Idealized Throat model that is independent of inspiratory flow rate and relative humidity. Largely eliminating URT deposition with a particle size larger than solution pMDIs is expected to improve delivery to the large and small airways, while minimizing alveolar deposition and particle exhalation.

Possibility of Use of NCC-Reinforced Melamine-Urea- Formaldehyde Adhesive in Plywood Manufacturing

The possibility of using nanocellulose (NCC) as a filling substance for melamine-urea-formaldehyde (MUF) adhesive was investigated for the process of manufacturing plywood. The adhesive mixtures were prepared with various nanocellulose concentrations. The amount of introduced filler had a significant effect on both resin and plywood characteristics. Fourier transform infrared spectroscopy (FTIR) did not show any major changes between experimental and reference variants. The viscosity of resin increased after the introduction of nanocellulose. The addition of NCC in the amount of 5 g and 10 g per 100 g of solid resin led to an improvement in bonding quality, modulus of elasticity and bending strength. Further increase of NCC concentration caused a deterioration of manufactured plywood properties. In summary, the addition of proper amount of nanocellulose resulted in manufacturing plywood with improved properties.

Mannitol Polymorphs as Carrier in DPIs Formulations: Isolation Characterization and Performance

The search for best performing carriers for dry powder inhalers is getting a great deal of interest to overcome the limitations posed by lactose. The aerosolization of adhesive mixtures between a carrier and a micronized drug is strongly influenced by the carrier solid-state properties. This work aimed at crystallizing kinetically stable D-mannitol polymorphs and at investigating their aerosolization performance when used in adhesive mixtures with two model drugs (salbutamol sulphate, SS, and budesonide, BUD) using a median and median/high resistance inhaler. A further goal was to assess in vitro the cytocompatibility of the produced polymer-doped mannitol polymorphs toward two lung epithelial cell lines. Kinetically stable (up to 12 months under accelerate conditions) α, and δ mannitol forms were crystallized in the presence of 2% w/w PVA and 1% w/w PVP respectively. These solid phases were compared with the β form and lactose as references. The solid-state properties of crystallized mannitol significantly affected aerosolization behavior, with the δ form affording the worst fine particle fraction with both the hydrophilic (9.3 and 6.5%) and the lipophilic (19.6 and 32%) model drugs, while α and β forms behaved in the same manner (11–13% for SS; 53–58% for BUD) and better than lactose (8 and 13% for SS; 26 and 39% for BUD). Recrystallized mannitol, but also PVA and PVP, proved to be safe excipients toward lung cell lines. We concluded that, also for mannitol, the physicochemical properties stemming from different crystal structures represent a tool for modulating carrier-drug interaction and, in turn, aerosolization performance.

Bio-based adhesive mixtures of pine tannin and different types of lignins

Tannins and lignins, which are natural phenolic compounds, are gaining substantial interest in biobased wood adhesive research. In this study, several different biobased tannin-lignin-hexamine adhesive mixtures were prepared and compared in a lap-joint shear strength test. In the first part, the suitability of different types of kraft and organosolv lignins as part of the mixture used in the production of biobased adhesives (in combination with pine tannins) were observed. It was found that biobased adhesive mixtures containing kraft lignins performed significantly better than those that contained organosolv lignins. In the second part, unmodified kraft lignins were mixed with pine tannin in different proportions, ranging from 0% to 100%. The pressing parameters were set to 150 °C for 15 min after performing oscillatory tests with a rheometer. Pure tannin adhesives performed the best, but no significant differences or a trend line were observed among adhesives containing different proportions of tannins and lignins.

Effect of alternative solvent evaporation techniques on mechanical properties of primer–adhesive mixtures.

This study evaluated the influence of the mode and time of solvent evaporation on the tensile strength (TS), flexural strength (FS) and elastic modulus (EM) of two adhesive systems: Scotchbond Multipurpose (SBMP) and Clearfil SE (CSEB). For this purpose, rectangular samples (2x1x7 mm) were prepared with 10 μL of primer and the solvents were evaporated with air spray at (23±1) ºC, (40±1) ºC and negative control (without spray). For each temperature, the times of 5, 20, 30, and 60 seconds were investigated. The statistical results showed that evaporation at 40±1ºC resulted in better EM for the two adhesives tested and all the evaporation times evaluated. However, there were no significant differences between the times and modes of evaporation for TS. The results of this study indicate that evaporation at a temperature of (40±1) °C could improve the elastic modulus of both adhesives tested, regardless of the evaporating time.