title: Feasibility of highly branched cyclic dextrin as an excipient matrix in dry powder inhalers.
abstract: 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.
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kadota
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Arisa
authors.initials: A
authors.lastname: Senda
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ito
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. Electronic address: ytozuka@gly.oups.ac.jp.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tozuka
mesh_terms: D000280:Administration, Inhalation; D000995:Antitubercular Agents / Q000008:administration & dosage; D003912:Dextrins / Q000008:administration & dosage* / Q000648:ultrastructure; D058995:Dry Powder Inhalers / Q000379:methods*; D005079:Excipients / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders / Q000008:administration & dosage; D012293:Rifampin / Q000008:administration & dosage
chemical_list: D000995:Antitubercular Agents; D003912:Dextrins; D005079:Excipients; D011208:Powders; D012293:Rifampin
keywords: 1-naphthocic acid; Composite particles; Fluorescence spectra; Rifampicin; Spray-drying