rifampin and 1-naphthoic-acid

　For efficient and deeper drug delivery into the lungs via dry powder inhalers (DPIs), we designed porous spray-dried particles (SDPs) containing anti-tuberculosis drugs and sugar-based excipients. The SDPs were prepared by spray-drying ethanol solutions containing isoniazid and/or rifampicin and sucrose, maltose, or highly branched cyclic dextrin (HBCD). Solid-state fluorescence emission spectroscopy showed that 1-naphthoic acid (1-NPA), a model drug, was dispersed in a molecular dispersion/solid solution, suggesting high potential of HBCD as an excipient in DPIs. 1-NPA was dispersed not only as active pharmaceutical ingredient (API) molecules with HBCD, but also as fine crystals. Morphological examination showed that the fine particles of HBCD/anti-tuberculosis drugs were porous, indicating high aerodynamic performance. Isoniazid and rifampicin could also be incorporated into the HBCD matrix. HBCD formulations exhibited higher released doses and fine-particle fractions than sucrose and maltose formulations, and could incorporate both hydrophilic and hydrophobic drugs.

Topics: Administration, Inhalation; Antitubercular Agents; Carboxylic Acids; Dextrins; Drug Compounding; Drug Delivery Systems; Drug Design; Dry Powder Inhalers; Ethanol; Excipients; Humans; Hydrophobic and Hydrophilic Interactions; Isoniazid; Maltose; Naphthalenes; Particle Size; Porosity; Powders; Rifampin; Solutions; Sucrose