(298h) Surface Modification to Improve Drug-Excipient Mixing for DPI Formulation

Recent advances in inhaled pulmonary and anti-microbial therapies using dry powder inhaler (DPI) has the limitation of blend homogeneity and uniform dose due to the cohesive nature of very fine drug particles. This study emphasizes the influence of API-excipient interaction on physical mixing for DPI formulation. Aceclofenac and lactose monohydrate are used for preparing blends by varying drug loading (1, 5, 10, 14, 20, 33 wt. %). Some of the blends are further modulated by surface modification of lactose with 1 wt. % nano-silica (R972 type). The quality of mixing is predicted by surface energy approach using work of adhesion/cohesion and Mixing Index (M.I.) is calculated using Reverse Phase-High Performance Liquid Chromatography (RP-HPLC). The morphology of drug, excipient and their blends were observed by Field Emission Scanning Electron Microscopy (FESEM). The flow property of the blend was determined using FT4 Rheometer. While the crystal level changes were observed using Powder X-Ray Diffraction (P-XRD), the physicochemical interaction between aceclofenac and lactose was confirmed by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC). The results show that M.I. is high for blends with high work of adhesion. Interestingly for all blends without any surface modification shows that there is a dip in M.I.when drug loading is in the range of 10 to14 wt. %. Also, Liquid Chromatography-Mass Spectroscopy (LC-MS) results confirm the presence of formation of the condensed compound. The surface coating over the lactose changes the inter-particle interactions. The results of coated blend showed improved mixing along with high flow function coefficient which is effective for pulmonary drug delivery. Moreover, there is an indication that the blends with surface modified lactose are more stable due to partial attachments of nano-particles on some of the most active sites on the lactose surface.