Abstract
The main purpose of this research was to compare the in vitro deposition efficiency and efficacy of dry powder inhalations and nebulized solutions of vancomycin hydrochloride. Dry powder inhalations of vancomycin hydrochloride were prepared by spray drying solutions of VH in water at different concentrations (5 and 50 mg/mL) and at different spray flow rates (30-60mm) with other parameters constant. The spray dried (SD) powders were characterized by determining the moisture content, particle size, endothermic events and surface morphology of the powder. The spray drying process yielded dry powders that had residual moisture content consistent with that of the commercial powder before spray drying. The SD powders exhibited narrower particle size distributions compared to the commercial powder. VH did not show any change in its physical nature after the spray drying process and this was confirmed by the differential scanning calorimetry. Scanning electron microscopy revealed that SD particles were loose aggregates of porous spheres. Nebulized solutions of VH were prepared in normal saline (20 mg in 5 ml). The osmolality and pH of the VH solution was found to be within the acceptable limits set for nebulized solutions.|The SD powders (20mg) were filled in capsules for aerosolization using an Aerolizer Inhaler dry powder inhaler device while nebulized aerosols were generated using an Aeroneb Pro® vibrating mesh nebulizer. The in vitro aerodynamic profile of SD powders was determined using a Next Generation Impactor (NGI) at flow rate of 60L/min and compared to a flow rate of 15L/min for nebulized solutionsIt was found that SD VH powders had smaller mass median aerodynamic diameters (MMAD) and higher percentages of fine particle fraction (%FPF) and thus better in vitro deposition efficiency than the nebulized solution of VH.|The anti-bacterial efficacy of SD and commercial VH powder was determined using Methicillin-resistant Staphylococcus aureus (MRSA) cultures. The SD VH powders had equivalent antibacterial efficacy as compared to commercial VH powder, indicating that VH retained its therapeutic activity and that the spray drying process did not degrade VH. The research also established a proof of concept for an in vitro Next Generation Impactor (NGI) model which could be used for screening aerosolized antibiotics. A deep collection cup was custom made in order to accommodate the surface of bacterial cultures at a depth as specified in the USP. The NGI was operated normally but with the normal Stage 4 collection cup replaced by the modified deep collection cup. VH solution was nebulized at flow rate of 15L/min and the percentage of dose deposited in all the stages was determined with no statistically significant difference (p>0.05) in the deposited dose percentage at Stage 4 between normal and modified collection cups.|A MRSA culture was then incorporated in the modified collection cup and placed inside the NGI. The nebulization of VH solution (20 mg in 5 ml) resulted in complete inhibition of bacterial colonies in the bacterial culture plate. A proof of concept for an in vitro NGI model which could test the in vitro deposition efficiency and anti-bacterial efficacy of nebulized VH solution using a modified deep collection cup was successfully developed.