Document Detail


Development of liposomal amphotericin B dry powder inhaler formulation.
MedLine Citation:
PMID:  15371106     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The purpose of our study was to prepare and optimize liposomal Amphotericin B (AMB) dry powder inhaler (DPI) formulation for treatment of invasive lung fungal infection. Liposomes were prepared by reverse phase evaporation technique using ethyl acetate and ethanol (1:1) as organic solvents to avoid a possible risk for human health and to impart adequate stability of the vesicles. Drug lipid ratio was 1:10 with membrane composition of hydrogenated soyaphosphatidylcholine; cholesterol and either saturated soyaphosphatidylglycerol (7:3:0.5) or stearylamine (1:1:0.1) was used to prepare negatively (AMB1) and positively (AMB2) charged liposomes, respectively. Liposomes were extruded through 2 microm polycarbonate membrane, separated from unentrapped drug and subjected to lyophilization using Tris buffer containing cryoprotectants in various mass ratios. Sucrose was found to be the best cryoprotectant for liposomal AMB in a mass ratio of lipid: sucrose at 1:5 for AMB1 and AMB2, respectively. Sorbolac 400 and sieved Pharmatose 325 M (500#) in varying mass ratios were used as carriers to prepare the liposomal DPI formulations and subjected to determination of angle of repose, compressibility index, dispersiblity index, water content, scanning electron microscopy, and fine particle fraction (FPF). Carrier blend of Sorbolac 400 and 10% sieved Pharmatose 325 M (liposome: carrier ratio to be 1:6) resulted in 22.6 +/- 2.2% and 16.8 +/- 2.2% FPF for AMB1 and AMB2, respectively with significantly different (p >.05) device fraction. Percent dug retention studies were conducted at different storage conditions and demonstrated a shelf life over 1 year at refrigerated storage condition (2-8 degrees C).
Authors:
S P Shah; Ambikanandan Misra
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Drug delivery     Volume:  11     ISSN:  1071-7544     ISO Abbreviation:  Drug Deliv     Publication Date:    2004 Jul-Aug
Date Detail:
Created Date:  2004-09-16     Completed Date:  2005-01-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9417471     Medline TA:  Drug Deliv     Country:  England    
Other Details:
Languages:  eng     Pagination:  247-53     Citation Subset:  IM    
Affiliation:
Pharmacy Department, Faculty of Technology and Engineering, Kalabhavan, M. S. University of Baroda, Gujarat, India.
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MeSH Terms
Descriptor/Qualifier:
Administration, Inhalation
Amphotericin B / administration & dosage,  chemistry*,  pharmacokinetics*
Chemistry, Pharmaceutical
Liposomes
Powders
Chemical
Reg. No./Substance:
0/Liposomes; 0/Powders; 1397-89-3/Amphotericin B

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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