Document Detail


Dissolution behavior of porcine somatotropin with simultaneous gel formation and lysine Schiff-base hydrolysis.
MedLine Citation:
PMID:  11689264     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The primary goal of this work was to develop a reliable in vitro dissolution model to evaluate the effects of Schiff-base hydrolysis and gel formation on the dissolution kinetics of pellets of porcine somatotropin (pST) and pST conjugated with ortho-vanillin (ov-pST) via Schiff-base formation, in an effort to develop an extended-release pST implant. Experimentally, dissolution was investigated as a function of ov concentration in pH 7.4, phosphate buffered saline under sink conditions where steady-state (constant flux) dissolution is typically observed. However, the resulting dissolution profiles displayed variable release rates due to gel formation at the solid-liquid interface, which impeded pST release. Chemical modification of pST with ov reduced gel formation and also resulted in much lower release rates. A mathematical model was developed that quantitatively accounts for changes in dissolution rates due to transient gel formation via irreversible aggregation, along with the effects of reversible Schiff-base hydrolysis involving ov, and predicts dissolution rates in the presence of ov decrease due to the much lower solubility of ov-pST. Our results indicate that although ov-pST is less prone to aggregate, pST/ov-pST equilibration is rapid compared to dissolution and therefore aggregation remains the limiting factor, and ultimately precludes this approach as a viable extended-release delivery system.
Authors:
C J Roberts; Q Ji; L Zhang; R T Darrington
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of controlled release : official journal of the Controlled Release Society     Volume:  77     ISSN:  0168-3659     ISO Abbreviation:  J Control Release     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-05     Completed Date:  2002-01-07     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  8607908     Medline TA:  J Control Release     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  107-16     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical R&D, MS# 8156-16, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. christopher_j_roberts@groton.pfizer.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Gels
Human Growth Hormone / chemistry*
Hydrolysis
Lysine
Schiff Bases
Solubility
Swine
Chemical
Reg. No./Substance:
0/Gels; 0/Schiff Bases; 12629-01-5/Human Growth Hormone; 56-87-1/Lysine

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


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