Document Detail


Low-temperature micronization of a peptide drug in fluid propellant: case study cetrorelix.
MedLine Citation:
PMID:  14727871     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Aim of this study was to elaborate an efficient method for the micronization of the decapeptide cetrorelix (a GnRH-antagonist), in order to obtain a microsuspension as basis for other pharmaceutical preparations, such as e.g. inhalation aerosols. A modified pearl-mill coupled with a cryostat was used for the micronization of cetrorelix in fluid propellant and operated under different conditions. The obtained cetrorelix suspensions were analyzed for particle size distribution, purity of cetrorelix, and for metal contamination through abrasion from parts of the mill. The method allowed an effective micronization of cetrorelix. The mean particle size of the initial cetrorelix lyophilizate bulk ware was reduced from 52.5 microm (Volume Mean Diameter, VMD) down to 14.9, 6.1 and 3.1 microm, respectively, respectively. The HPLC analysis of all cetrorelix suspensions after micronization did not show signs of decomposition as compared to the initial product. The elementary analysis of the suspensions performed by inductively coupled plasma mass spectrometry revealed a negligible amount of contaminants in the suspension (Zr = max. 0.6 ppm; Fe, Cr, Ni, Ba, below limit of quantification, i.e. < 0.14 ppm). The only appreciable contaminant, Aluminum (Al = 1.1 ppm), was derived from the mechanical capping of aluminum canisters prior to analysis. The Zr determination in the suspension of 0.6 ppm, is still considered to be negligible as compared to the legally tolerated limit of air contamination. By low-temperature micronization in fluid propellant, fine drug suspensions of cetrorelix for pMDIs can be directly manufactured in one-step procedure without destruction of the peptide structure and without appreciable product contamination.
Authors:
R Lizio; M Damm; A W Sarlikiotis; H H Bauer; C M Lehr
Publication Detail:
Type:  Journal Article     Date:  2001-07-12
Journal Detail:
Title:  AAPS PharmSciTech     Volume:  2     ISSN:  1530-9932     ISO Abbreviation:  AAPS PharmSciTech     Publication Date:  2001  
Date Detail:
Created Date:  2004-01-19     Completed Date:  2004-04-15     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  100960111     Medline TA:  AAPS PharmSciTech     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E12     Citation Subset:  IM    
Affiliation:
Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, 66123 Saarbrücken, Germany. rosario_lizio@roehm.com
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MeSH Terms
Descriptor/Qualifier:
Administration, Inhalation
Aerosol Propellants
Freezing
Gonadotropin-Releasing Hormone / administration & dosage*,  analogs & derivatives*,  chemistry,  metabolism
Hormone Antagonists / administration & dosage*,  chemistry,  metabolism
Hydrocarbons, Fluorinated
Metals / analysis
Particle Size
Suspensions / chemistry
Chemical
Reg. No./Substance:
0/Aerosol Propellants; 0/Hormone Antagonists; 0/Hydrocarbons, Fluorinated; 0/Metals; 0/Suspensions; 33515-09-2/Gonadotropin-Releasing Hormone; 431-89-0/HFA 134a; OON1HFZ4BA/cetrorelix

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


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