Engineering of levodopa inhalable microparticles in combination with leucine and dipalmitoylphosphatidylcholine by spray drying technique

The aim of this work was to study the effect of concomitant use of leucine and dipalmitoylphosphatidylcholine, in different ratios, on aerosolization performance of levodopa. Three-component formulations were selected based on a central composite design using percentages of leucine and dipalmitoylphosphatidylcholine as the independent variables. Particle size, surface roughness index, surface phosphorus and fine particle fraction were considered as dependent variables in the model. The spray dried samples were also characterized to determine their particle shape and solid state nature. levodopa was spray dried with 10–40% w/w of the excipients to prepare two- or three-component formulations. A crystalline nature was determined for levodopa in all samples spray dried from water:ethanol (30:70 v/v). Roughness in surface of the processed particles increased with increasing total concentration of the excipients, specially above 25% w/w. Analysis of phosphorus on the surface demonstrated that three-component formulations prepared with combination of 12.5% w/w leucine had the highest amount of dipalmitoylphosphatidylcholine in the surface, regardless of its percentage used in the initial feed. A combination of 12.43% w/w of leucine and 9.80% w/w of dipalmitoylphosphatidylcholine used in formulation exhibited the highest fine particle fraction (72.63%). It can be concluded that spray drying of levodopa with a suitable combination of both excipients leads to production of a three-component formulation of crystalline levodopa, with an aerosolization performance which is significantly higher than two-component formulations composed of the drug with either leucine or dipalmitoylphosphatidylcholine. [Display omitted]