| Application of a four-fluid nozzle spray drier to prepare inhalable rifampicin-containing mannitol microparticles. | |
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MedLine Citation:
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PMID: 18563576 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The purpose of this study was to use a four-fluid nozzle spray drier as a new one-step method for preparing rifampicin (RFP)-containing mannitol microparticles. A RFP-acetone/methanol (2:1) solution and aqueous solutions of mannitol (MAN) were simultaneously supplied through different liquid passages of a four-fluid nozzle spray drier and then dried to obtain MAN microparticles containing RFP. Using a cascade impactor, the in vitro aerosol performance of RFP powder and RFP-MAN microparticles with 1:5, 1:10, and 1:20 ratios was compared. The in vivo retention of RFP in the lungs of rats after intratracheal administration of 1:20 RFP-MAN microparticles was also compared. The RFP-MAN microparticles had better aerosol performance than RFP powder and delivery to the lung stages improved as the fraction of MAN was increased. For the 1:20 RFP-MAN microparticles, deposition in stages 2-7 was approximately 43%, which is sufficient for treatment. Approximately 8% of the RFP-MAN microparticles were deposited in stages 6-7, which corresponds to alveoli containing alveolar macrophages. The initial retention of RFP in the lung following pulmonary delivery of 1:20 RFP-MAN microparticles was higher than following oral or intravenous administration of RFP, but the elimination was rapid, resulting in the disappearance of RFP from the lung within 4 h. The plasma concentration-time profile of RFP after intratracheal administration of 1:20 RFP-MAN microparticles was consistent with the profile for RFP retention in the lung. Addition of cholesterol or phosphatidylcholine to RFP had little effect on its retention in the lung. The RFP-MAN microparticles were effective for delivery of RFP to the lung, but the RFP rapidly removed from the lung into the blood circulation. This study demonstrated that RFP-containing MAN microparticles prepared in one step using the four-fluid nozzle spray drier efficiently deliver RFP to the lung, although methods must be developed to prolong its retention and improve targeting to alveolar macrophages. |
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Authors:
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Takuto Mizoe; Tetsuya Ozeki; Hiroaki Okada |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2008-06-18 |
Journal Detail:
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Title: AAPS PharmSciTech Volume: 9 ISSN: 1530-9932 ISO Abbreviation: AAPS PharmSciTech Publication Date: 2008 |
Date Detail:
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Created Date: 2008-10-27 Completed Date: 2009-05-13 Revised Date: 2011-07-27 |
Medline Journal Info:
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Nlm Unique ID: 100960111 Medline TA: AAPS PharmSciTech Country: United States |
Other Details:
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Languages: eng Pagination: 755-61 Citation Subset: IM |
Affiliation:
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Laboratory of Pharmaceutics and Drug Delivery, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Inhalation Aerosols / administration & dosage, chemical synthesis Animals Chemistry, Pharmaceutical / instrumentation, methods* Desiccation Drug Delivery Systems / methods Lung / drug effects, metabolism Male Mannitol / administration & dosage, chemical synthesis* Particle Size Rats Rats, Sprague-Dawley Rifampin / administration & dosage, chemical synthesis* |
| Chemical | |
Reg. No./Substance:
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0/Aerosols; 13292-46-1/Rifampin; 69-65-8/Mannitol |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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