Document Detail


Crystallization of progesterone for pulmonary drug delivery.
MedLine Citation:
PMID:  19691108     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The purpose of this study is to investigate the suitability of the crystallization process to produce microcrystals of progesterone for respiratory drug delivery. Crystallization of progesterone was carried out from water-isopropanol (IPA) mixture. The antisolvent (water) was added at two different addition rates (10 and 100 mL/min). The mass percentage of antisolvent was varied between (50% and 75%), and the initial drug concentration was adjusted at (0.5 and 1 g/L). The effect of crystallization method (antisolvent precipitation or combined cooling and antisolvent) was also examined. These operating conditions were investigated in a 2(4) factorial design in an effort to optimize the process. Different solid-state and surface characterization techniques were applied in conjunction with measurements of powder flow properties using aerodynamic particle sizer (APS). Powder dispersibility and aerosol performance were analyzed using Anderson Cascade Impactor (ACI). Antisolvent addition rate, initial drug concentration and dynamic solvent composition are shown to have a significant effect on the aerosol characteristics of progesterone microcrystals. An increase of 38.73% in the fine particle fraction (FPF) was demonstrated for some powders produced by combined cooling and antisolvent crystallization. In conclusion, it was possible to control particle size and hence, pulmonary deposition using process parameters alone, and produce particles with a narrow particle size distribution and a mean particle size of 5 microm with nearly no particles larger than 10 microm by direct crystallization. The suitability of deep pulmonary deposition was proved by the platelet-like morphology of processed microcrystals and greater surface-to-volume ratio than spherical particles.
Authors:
Doaa Ragab; Sohrab Rohani; Magda W Samaha; Ferial M El-Khawas; Hoda A El-Maradny
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  99     ISSN:  1520-6017     ISO Abbreviation:  J Pharm Sci     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-01-19     Completed Date:  2010-04-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1123-37     Citation Subset:  IM    
Copyright Information:
2009 Wiley-Liss, Inc. and the American Pharmacists Association
Affiliation:
Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, Ontario, Canada N6A 5B9.
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MeSH Terms
Descriptor/Qualifier:
Administration, Inhalation
Aerosols / chemistry
Chemistry, Pharmaceutical / methods
Crystallization / methods*
Drug Delivery Systems / methods*
Drug Stability
Models, Chemical
Models, Statistical
Particle Size
Powders / chemistry
Progesterone / administration & dosage,  chemistry*
Technology, Pharmaceutical / instrumentation,  methods*
Chemical
Reg. No./Substance:
0/Aerosols; 0/Powders; 57-83-0/Progesterone

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


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