Document Detail


Hydroxypropyl methylcellulose acetate succinate: potential drug-excipient incompatibility.
MedLine Citation:
PMID:  18758966     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The stability of hydroxypropyl methylcellulose acetate succinate (HPMC-AS) and its potential incompatibility with active pharmaceutical ingredients (API) carrying hydroxyl group(s) were investigated in this research. HPMC-AS may undergo hydrolysis under harsh processing conditions with the generation of succinic acid and acetic acid, which can form ester bond(s) with the hydroxyl group(s) in API. In this case, the hot-melt extrusion (HME) product prepared from HPMC-AS and our model compound (compound A) was tested after heating at 140 degrees C up to 5 h. The succinate esters of compound A and its epimer were found in the product, suggesting potential drug-excipient incompatibility during formulation development. In addition, dyphylline was also tested with HPMC-AS and the potential incompatibility was further confirmed.
Authors:
Zedong Dong; Duk Soon Choi
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Publication Detail:
Type:  Journal Article     Date:  2008-08-29
Journal Detail:
Title:  AAPS PharmSciTech     Volume:  9     ISSN:  1530-9932     ISO Abbreviation:  AAPS PharmSciTech     Publication Date:  2008  
Date Detail:
Created Date:  2008-10-27     Completed Date:  2009-05-13     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  100960111     Medline TA:  AAPS PharmSciTech     Country:  United States    
Other Details:
Languages:  eng     Pagination:  991-7     Citation Subset:  IM    
Affiliation:
Pharmaceutical and Analytical Research and Development, Hoffmann-La Roche, Inc., 340 Kingsland Street, Nutley, New Jersey 07110, USA. zedong_dong@yahoo.com
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MeSH Terms
Descriptor/Qualifier:
Chemistry, Pharmaceutical
Chromatography, Liquid
Drug Incompatibility*
Dyphylline / analysis,  chemistry
Esterification
Excipients / analysis,  chemistry*
Hydrolysis
Methylcellulose / analogs & derivatives*,  analysis,  chemistry
Tandem Mass Spectrometry
Chemical
Reg. No./Substance:
0/Excipients; 479-18-5/Dyphylline; 71138-97-1/hydroxypropylmethylcellulose acetate succinate; 9004-67-5/Methylcellulose
Comments/Corrections

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