Formation of peptide impurities in polyester matrices during implant manufacturing

Most peptides are susceptible, in vivo, to proteolytic degradation, and it is difficult to formulate and to deliver them without loss of biological activity. In addition, it is often desirable to release them continuously and at a controlled rate over a period of weeks or months. For these reasons,...

Full description

Saved in:
Bibliographic Details
Published in:European journal of pharmaceutics and biopharmaceutics 2000-05, Vol.49 (3), p.253-257
Main Authors: Rothen-Weinhold, A, Oudry, N, Schwach-Abdellaoui, K, Frutiger-Hughes, S, Hughes, G.J, Jeannerat, D, Burger, U, Besseghir, K, Gurny, R
Format: Article
Language:English
Subjects:
Analgesics - administration & dosage
Analgesics - chemistry
Drug Compounding
Drug Contamination
Drug Delivery Systems
Drug Implants - chemistry
Impurity
Lactic Acid
Magnetic Resonance Spectroscopy
Mass Spectrometry
Melt-processing
Peptide
Peptides - chemistry
Polyesters
Polylactic acid
Polymers
Somatostatin - administration & dosage
Somatostatin - analogs & derivatives
Somatostatin - chemistry
Vapreotide
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Most peptides are susceptible, in vivo, to proteolytic degradation, and it is difficult to formulate and to deliver them without loss of biological activity. In addition, it is often desirable to release them continuously and at a controlled rate over a period of weeks or months. For these reasons, a controlled release system is suitable. Poly(lactic acid) (PLA) is a biocompatible and biodegradable material that can be used for many applications, including the design of injectable controlled release systems for pharmaceutical agents. Development of these delivery systems presents challenges in the assessment of stability, specially for peptide drugs. By means of an extrusion method, long-acting poly(lactic acid) implants containing vapreotide, a somatostatin analogue, were prepared. The nature of the main degradation product obtained after implant manufacturing was elucidated. It was found that the main peptide impurity was a lactoyl lactyl–vapreotide conjugate. Because lactide are found in small quantities in most commercially available PLA, the influence of residual lactide in the polymeric matrix, on the formation of peptide impurities during manufacturing, was specially investigated. This work demonstrates that the degree of purity of the carrier is of great importance with regard to the formation of peptide impurities.
ISSN:0939-6411
1873-3441
DOI:10.1016/S0939-6411(00)00066-7