We investigated the feasibility of highly branched cyclic dextrin (HBCD) as an excipient matrix in dry powder inhalers (DPIs). The fine particles of HBCD and HBCD/active pharmaceutical ingredients (APIs) were prepared by spray-drying an ethanol-aqueous solution containing HBCD. The particle size of spray-dried HBCD itself was approximately 3.0μm with a wrinkled shape. Solid-state fluorescence emission spectroscopy of 1-naphthoic acid (1-NPA) showed that it was dispersed in a molecular dispersion/solid solution, if the model compound of 1-NPA was spray-dried with HBCD. Powder X-ray diffraction and differential scanning calorimetry indicate that 1-NPA was in the amorphous state after spray-drying with HBCD, which is confirmed by the fluorescence measurements, 1-NPA could be incorporated into HBCD. When the antimycobacterial agent, rifampicin, was spray-dried with HBCD for the purpose of pulmonary administration, the emitted dose and fine-particle fraction of the spray-dried particles of rifampicin with HBCD were 95.7±1.7% and 39.5±5.7%, respectively. The results indicated that HBCD possessed a high potential as an excipient in DPIs, not only by molecular association of API molecules with HBCD, but also by that of API fine crystals.
Keywords: 1-naphthocic acid; Composite particles; Fluorescence spectra; Rifampicin; Spray-drying.
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