Document Detail

Crosslinking studies in gelatin capsules treated with formaldehyde and in capsules exposed to elevated temperature and humidity.
MedLine Citation:
PMID:  11064381     Owner:  NLM     Status:  MEDLINE    
Incomplete in vitro capsule shell dissolution and subsequent drug release problems have recently received attention. A modified USP dissolution method was used to follow capsule shell dissolution, and a 2,4,6-trinitrobenzenesulfonic acid (TNBS) assay was used to follow loss of epsilon-amino groups to study this shell dissolution problem postulated to be due to gelatin crosslinking. The dissolution problems were simulated using hard gelatin capsule (HGC) shells previously treated with formaldehyde to crosslink the gelatin. These methods were also used to study the effect of uncrosslinked HGC stored under stressed conditions (37 degrees C and 81% RH) with or without the presence of soft gelatin capsule shells (SGC). A 120 ppm formaldehyde treatment reduced gelatin shell dissolution to 8% within 45 min in water at 37 degrees C. A 200 ppm treatment reduced gelatin epsilon-amino groups to 83% of the original uncrosslinked value. The results also support earlier reports of non-amino group crosslinking by formaldehyde in gelatin. Under stressed conditions, HGC stored alone showed little change over 21 weeks. However, by 12 to 14 weeks, the HGC exposed to SGC showed a 23% decrease in shell dissolution and an 8% decrease in the number of epsilon-amino groups. These effects on the stressed HGC are ascribed to a volatile agent from SGC shells, most likely formaldehyde, that crosslinked nearby HGC shells. This report also includes a summary of the literature on agents that reduce gelatin and capsule shell dissolution and the possible mechanisms of this not-so-simple problem.
C M Ofner; Y E Zhang; V C Jobeck; B J Bowman
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  90     ISSN:  0022-3549     ISO Abbreviation:  J Pharm Sci     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-01-26     Completed Date:  2001-05-31     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  79-88     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90: 79-88, 2001
Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, 600 South 43rd Street, Philadelphia, Pennsylvania 19104, USA.
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MeSH Terms
Aldehydes / chemistry
Capsules / chemistry
Coloring Agents / chemistry
Cross-Linking Reagents / chemistry*
Formaldehyde / chemistry
Gelatin / chemistry*
Grant Support
FDA-223-95-3006/FD/FDA HHS
Reg. No./Substance:
0/Aldehydes; 0/Capsules; 0/Coloring Agents; 0/Cross-Linking Reagents; 50-00-0/Formaldehyde; 9000-70-8/Gelatin

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

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