Self-Assembly of Polyion–Surfactant Ion Complex Salts in Mixtures with Water and n-Alcohols

Phase behavior and structural features were investigated for "complex salts", consisting of the cationic hexadecyltrimethylammonium (CTA) surfactant with polyacrylate (PA(n), n = 30 or 6000) counterions, mixed with water and different n-alcohols (ethanol, butanol, hexanol, octanol, and decanol). The liquid crystalline structures formed were identified by small-angle X-ray scattering measurements, which provided information about the changes in the geometry of the aggregates as functions of the concentration and chain length of the added n-alcohol. The obtained results were compared with a previous work on similar ternary mixtures of the same cationic surfactant but with the monomeric bromide counterion, CTABr (Fontell, K; Khan, A.; Lindstrom, B.; Maciejewska, D.; Puang-Ngem, S. Colloid Polym. Sc., 1991, 269, 727). In general, the same phases were detected in systems with the complex salts CTAPA(n) as in systems with CTABr, but the swelling of the various liquid crystalline phases by water was much more limited in the complex salt systems. An isotropic alcoholic phase was observed with all alcohols and the size of this region of the phase diagram increased for the shorter alcohols, except for ethanol. For mixtures with octanol and ethanol, in particular, the extensions of the disordered isotropic phases were larger for the complex salt with the shorter polyacrylate ions

Agglomerated novel spray-dried lactose-leucine tailored as a carrier to enhance the aerosolization performance of salbutamol sulfate from DPI formulations

Spray-drying allows to modify the physicochemical/mechanical properties of particles along with their morphology. In the present study, L-leucine with varying concentrations (0.1, 0.5, 1, 5, and 10% w/v) were incorporated into lactose monohydrate solution for spray-drying to enhance the aerosolization performance of dry powder inhalers containing spray-dried lactose-leucine and salbutamol sulfate. The prepared spray-dried lactose-leucine carriers were analyzed using laser diffraction (particle size), differential scanning calorimetry (thermal behavior), scanning electron microscopy (morphology), powder X-ray diffraction (crystallinity), Fourier transform infrared spectroscopy (interaction at molecular level), and in vitro aerosolization performance (deposition). The results showed that the efficacy of salbutamol sulfate’s aerosolization performance was, in part, due to the introduction of L-leucine in the carrier, prior to being spray-dried, accounting for an increase in the fine particle fraction (FPF) of salbutamol sulfate from spray-dried lactose-leucine (0.5% leucine) in comparison to all other carriers. It was shown that all of the spray-dried carriers were spherical in their morphology with some agglomerates and contained a mixture of amorphous, α-lactose, and β-lactose. It was also interesting to note that spray-dried lactose-leucine particles were agglomerated during the spray-drying process to make coarse particles (volume mean diameter of 79 to 87 μm) suitable as a carrier in DPI formulations

Surface Deposition and Phase Behavior of Oppositely Charged Polyion–Surfactant Ion Complexes. Delivery of Silicone Oil Emulsions to Hydrophobic and Hydrophilic Surfaces

The adsorption from mixed polyelectrolyte-surfactant solutions at hydrophobized silica surfaces was investigated by in situ null-ellipsometry, and compared to similar measurements for hydrophilic silica surfaces. Three synthetic cationic copolymers of varying hydrophobicity and one cationic hydroxyethyl cellulose were compared in mixtures with the anionic surfactant sodium dodecylsulfate (SDS) in the absence or presence of a dilute silicone oil emulsion. The adsorption behavior was mapped while stepwise increasing the concentration of SDS to a polyelectrolyte solution of constant concentration. The effect on the deposition of dilution of the bulk solution in contact with the surface was also investigated by gradual replacement of the bulk solution with 1 mM aqueous NaCl. An adsorbed layer remained after complete exchange of the polyelectrolyte/surfactant solution for aqueous NaCl. In most cases, there was a codeposition of silicone oil droplets, if such droplets were present in the formulation before dilution. The overall features of the deposition were similar at hydrophobic and hydrophilic surfaces, but there were also notable differences. SDS molecules adsorbed selectively at the hydrophobized silica surface, but not at the hydrophilic silica, which influenced the coadsorption of the cationic polymers. The largest amount of deposited material after dilution was found for hydrophilic silica and for the least-hydrophobic cationic polymers. For the least-hydrophobic polyions, no significant codeposition of silicone oil was detected at hydrophobized silica after dilution if the initial SDS concentration was high

Simulation of dry powder inhalers: combining micro-scale, meso-scale and macro-scale modeling

The flow of carrier particles, coated with active drug particles, is studied in a prototype dry powder inhaler. A novel, multi-scale approach consisting of a discrete element model (DEM) to describe the particles coupled with a dynamic large eddy simulation (LES) model to describe the dynamic nature of the flow is applied. The model consists of three different scales: the micro-scale, the meso-scale and the macro-scale. At the micro-scale, the interactions of the small active drug particles with larger carrier particles, with the wall, with the air flow, and with each other is thoroughly studied using discrete element modelling and detailed computational fluid dynamics (CFD), i.e. resolving the flow structures around the particles. This has led to the development of coarse-grained models, describing the interaction of the small active drug particles at the larger scales. 1 At the meso-scale the larger carrier particles, and all of their interactions are modelled individually using DEM and CFD-LES. Collisions are modeled using a visco-elastic model to describe the local deformation at each point of particle-particle contact in conjunction with a model to account for cohesion. At the macro-scale, simulations of a complete prototype inhaler are carried out. By combining the relevant information of each of the scales, simulations of the inhalation of one dose from a prototype inhaler using a patient relevant air flow profile show that fines leave the inhaler faster than the carrier particles. The results also show that collisions are not important for particle-particle momentum exchange initially but become more important as the particles accelerate. It is shown that for the studied prototype inhaler the total release efficiency of the fine particles is between 10% and 30%, depending on the Hamaker constant, using typical settings for the properties of both particles. The results are also used to study regions of recirculation, where carrier particles can become trapped, and regions where fines adhere to the wall of the device