Degradation products toxicological evaluation

An example is poly(bis(p-carboxyphenoxy)propane) (PCPP) which has been prepared as a copolymer with various levels of sebacic anhydride (SA). Injection molded samples of poly (anhydride) / dmg mixtures display 2ero-order kinetics in both polymer erosion and dmg release. Degradation of these polymers simply releases the dicarboxyhc acid monomers (54). Preliminary toxicological evaluations showed that the polymers and degradation products had acceptable biocompatibiUty and did not exhibit cytotoxicity or mutagenicity (55). 

Within the analytical research and development (R D) unit, specifications and methods for clinical trial materials are approved and results from shortterm stability evaluations are reported. Method validation is completed for critical validation parameters for those methods used in release and stability testing of the clinical materials. Impurities and degradation products are tabulated for the toxicology and clinical batches to assure the safety of the materials for human use. 

A number of companion techniques have been shown to be useful and merit further use. These include NMR, IR, MS, GC-MS, AA, X-ray microscopy, and GPC. ESR has not been appreciably utilized as a companion technique but may be considered, particularly with polymers containing ESR-sensitive metals. Gel permeation chromatography (GPC) should be considered as a companion tool for thermal degradation evaluations where depolymerization is suspected. There is a need for a number of well-chosen thermal analysis studies of both the volatile products by TG-MS, etc. (for both chemical and toxicological purposes) and the residue. Such studies should occur throughout the studied temperature range rather than just at the room and final temperatures. 

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