(442e) Variation of Spray-Dried Levodopa-Loaded Microcarrier Properties in Correlation with L-Leucine Concentration

To counter the challenges of oral medication of Levodopa in patients of Parkinson’s Disease and utilize the advantages of pulmonary drug delivery, inhalable Levodopa formulations with high aerosolization are the need of the hour. The goal of the current work is to evaluate the effects of altering L-leucine concentrations in inhalable co-spray-dried lacto-polymeric Levodopa-loaded microcarriers on their physiochemical and aerosolization properties. Excipients such as a polymer, PLGA (65:35), a carbohydrate, α-Lactose Monohydrate and an amino acid, L-Leucine were selected. The spray-dried Levodopa-loaded microcarriers (LMCs) were then characterized to determine their particle size distribution, drug loading and entrapment efficiency, powder flowability, solid state nature, aerosolization properties and drug dissolution. Increase in L-leucine concentration from 0 to 1% showed a marked improvement in the drug entrapment efficiency (from 17% to 60%), in powder flowability (decrease in CI from 58% to 19%) while the particle size range was observed to decrease. With increasing L-leucine concentrations, PXRD results displayed an increase in the crystallinity of the Levodopa formulations while DSC data indicated an increase in the peak temperature of sublimation from 300°C to 425°C, thereby enhancing their thermostability. At 1% Leucine, aerosolization data showed the highest mean Emitted Dose and Fine Particle Fraction at 79% and 54% respectively. Sustained but similar drug release profiles were observed in simulated lung fluids with a cumulative Levodopa release of upto 85 to 90% achieved by the Hour 19 to 21 for formulations with 0.6% to 1 % Leucine concentration. Overall, it can be concluded that the concentration of L-leucine impacts the physicochemical characteristics and the aerosolization properties of inhalable Levodopa powders.