| Impurity formation studies with peptide-loaded polymeric microspheres Part II. In vitro evaluation. | |
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MedLine Citation:
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PMID: 15885939 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Since acylated peptide impurities were isolated from octreotide microspheres following incubation in an in vivo environment, the present investigation was undertaken to determine the dosage form dynamics responsible for facilitating acylation. In particular, microsphere batches made with poly(L-lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) 85:15 were studied for in vitro drug release, mass balance relationships, mass loss behavior, hydration uptake, and solid-state stability. Furthermore, native octreotide was incubated in a varying pH stability model (heat treated lactic acid solutions 42.5%, w/w) to determine the effects of acidity on impurity formation. From a review of the experimental results, the appearance of octreotide impurities or related substances occurred with the onset of polymeric mass loss. In fact, the significant formation of acylated peptide did not appear until >90% mass loss, which was observed at 14 days. It was surmised that because of water uptake, the hydrolytic cleavage of the polymeric backbone created an acidic microenvironment to facilitate the covalent coupling of peptide with polymer. The lactic acid solution stability model corroborated with greater evidence of acylation at pH 2.25 where the presence lactoyl (+72 m/z) derivatives of octreotide were confirmed by MALDI-TOF mass spectrometry. |
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Authors:
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Santos B Murty; Dong Hee Na; B C Thanoo; Patrick P DeLuca |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: International journal of pharmaceutics Volume: 297 ISSN: 0378-5173 ISO Abbreviation: Int J Pharm Publication Date: 2005 Jun |
Date Detail:
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Created Date: 2005-05-23 Completed Date: 2005-09-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7804127 Medline TA: Int J Pharm Country: Netherlands |
Other Details:
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Languages: eng Pagination: 62-72 Citation Subset: IM |
Affiliation:
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Murty Pharmaceuticals, Inc., Lexington, KY 40509, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acylation Buffers Chemistry, Pharmaceutical Chromatography, High Pressure Liquid Drug Compounding Drug Contamination* Drug Stability Excipients Hydrogen-Ion Concentration Lactic Acid Microspheres Octreotide / administration & dosage*, chemistry Peptides / administration & dosage*, chemistry Phosphates Polyesters Polyglycolic Acid Polymers Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Temperature |
| Chemical | |
Reg. No./Substance:
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0/Buffers; 0/Excipients; 0/Peptides; 0/Phosphates; 0/Polyesters; 0/Polymers; 0/polylactic acid-polyglycolic acid copolymer; 26009-03-0/Polyglycolic Acid; 26969-66-4/poly(lactide); 50-21-5/Lactic Acid; 83150-76-9/Octreotide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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