Document Detail


Impact milling of pharmaceutical agglomerates in the wet and dry states.
MedLine Citation:
PMID:  17804181     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study focused on the milling of wet granulated agglomerates at points before and after drying in a typical high-shear pharmaceutical process train. These steps, referred to here as wet and dry milling, utilized a conical screen mill. Milling of granulation in the wet state eliminated 1-10mm size agglomerates without affecting granule porosity or inducing further agglomeration. These millimeter-size agglomerates broke down during wet milling into moderately sized fragments larger than 125microm. In contrast, when milled after drying, these same 1-10mm-size agglomerates broke down predominantly into fine particles less than 125microm. Data from screen-less milling trials suggest that the mill screen served only as a classifier and did not significantly contribute to the route of breakage for either wet or dry milling. However, in the case of dry milling, mill screens with grated surface textures did result in fewer fines than non-grated screens. This may be a result of reduced residence time in the mill. Experiments varying the size fraction of feed material and the rotational speed of the mill's impeller identified impact attrition as the primary mechanism governing dry granule breakage. The findings in this study shed light into the fundamental breakdown behavior of pharmaceutical agglomerates and demonstrate how breakdown of wet agglomerates via a de-lumping step prior to drying can lead to a reduced level of fine particle generation during dry milling.
Authors:
Luke R Schenck; Russell V Plank
Publication Detail:
Type:  Journal Article     Date:  2007-07-27
Journal Detail:
Title:  International journal of pharmaceutics     Volume:  348     ISSN:  0378-5173     ISO Abbreviation:  Int J Pharm     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2007-12-24     Completed Date:  2008-04-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7804127     Medline TA:  Int J Pharm     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  18-26     Citation Subset:  IM    
Affiliation:
Pharmaceutical Technology, Merck & Co., Inc., West Point, PA 19486, USA. Luke_Schenck@Merck.com
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MeSH Terms
Descriptor/Qualifier:
Algorithms
Carboxymethylcellulose / chemistry
Cellulose / analogs & derivatives,  chemistry
Excipients / chemistry*
Lactose / chemistry
Mechanics
Particle Size*
Pharmaceutical Preparations / chemistry*
Povidone / chemistry
Powders / chemistry*
Water / chemistry
Chemical
Reg. No./Substance:
0/Excipients; 0/Pharmaceutical Preparations; 0/Powders; 0/microcrystalline cellulose; 63-42-3/Lactose; 7732-18-5/Water; 9003-39-8/Povidone; 9004-32-4/Carboxymethylcellulose; 9004-34-6/Cellulose; 9004-64-2/hydroxypropylcellulose

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


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