Feasibility of highly branched cyclic dextrin as an excipient matrix in dry powder inhalers

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 3.0 μm 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.

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