Dry Powder Inhalation Formulation of PLGA/PEG microparticles: Optimization of Spray Drying with the Box-Behnken Design

Abstract

Srushti J. Sodha and Pardeep K. Gupta

Large, porous microparticles have emerged as an attractive platform for pulmonary delivery of therapeutic proteins. While the large size and porosity imparts buoyancy and lung dispersibility, tailoring the polymer surface characteristics enables retention of protein stability and desirable release profile. Previously, we developed porous PLGA microparti- cles with PLGA 50501A and established stability and controlled release of Somatropin for 7 days. PEG was established as a multifunctional pore former – providing benefits of polymer plasticization, improved drug loading and stability. The goal of the current study is scaling up the system to obtain a robust, platform process for large scale manufacturing of porous PLGA/PEG microparticles with diameters between 5 – 12 μm, low densities (<0.4 g/cm3), high porosity using Buchi mini-spray dryer. Design of Experiments using Box-Behnken design was used to develop and validate a mathe- matical model correlating microparticle characteristics to the operation parameters.

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