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

Box-Behnken experimental design in the development of a nasal drug delivery system of model drug hydroxyurea: Characterization of viscosity, in vitro drug release, droplet size, and dynamic surface tension

The purpose of the research was to investigate the changes in physicochemical properties and their influence on nasal formulation performance using 5-factor, 3-level Box-Behnken experimental design on the combined responses of viscosity, droplet size distribution (DSD), and drug release. Gel formulations of hydroxyurea (HU) with surface-active polymers (hydroxyethylcellulose [HEC] and polyethylene-oxide [PEO]) and ionic excipients (sodium chloride and calcium chloride) were prepared using Box-Behnken experimental design. The rheology and dynamic surface tension (DST) of the test formulations was investigated using LV-DV-III Brookfield rheometer and T60 SITA tensiometer, respectively. Droplet size analysis of nasal aerosols was determined by laser diffraction using the Malvern Spraytec with the InnovaSystems actuator. In vitro drug release studies were conducted on Franz diffusion cells. With PEO gel, calcium chloride increased the viscosity and DSD and retarded drug release, while sodium chloride decreased the viscosity, DST, and DSD and accelerated the release of HU. With HEC gel, the addition of the above salts resulted in less significant changes in viscosity, DSD, and DST, but both salts significantly increased the release of HU. Droplet size data obtained from a high viscosity nasal pump was dependent on type of polymer, polymer-excipient interactions, and solvent properties. The applications of Box-Behnken experimental design facilitated the prediction and identified major excipient influences on viscosity, DSD, and in vitro drug release