EFFECTS OF PROCESSING ON THE SOLID-STATE METHYL TRANSFER OF TETRAGLYCINE METHYL-ESTER

The thermally induced solid-state methyl transfer of tetraglycine meth yl ester (TGME) was followed by HPLC analysis for samples subjected to freeze-drying and milling and compared to that observed for a highly crystalline unprocessed sample. Corresponding measurements by powder X -ray diffraction and differential scanning calorimetry were used to fo llow physical changes in these samples during the course of the reacti on. It was shown that freeze-drying and milling of TGME produced sampl es with significantly reduced crystallinity, i.e. amorphous structure, as well as an apparent polymorphic transformation. HPLC analysis reve aled greatly enhanced chemical reactivity for the processed samples re lative to the crystalline sample, but no overall change in the chemica l intermediates and products produced. The kinetic curves for the free ze-dried samples were monotonic and could be treated by a first-order model, whereas the curves for the milled samples consisted of two part s, a rapid initial reaction followed by a slow phase. Kinetic data in both cases were treated with the assumption that the reaction proceeds independently and simultaneously in amorphous and crystalline phases. It was shown that reactivity in the amorphous phase for freeze-dried and milled samples is very similar, whereas reactivity taking place in the crystalline regions occurs at a rate almost two orders-of-magnitu de greater in freeze-dried samples than in the milled preparations. Th us it is concluded that in addition to the formation of amorphous stat es processing of TGME such as freeze-drying or milling can introduce d isorder into the remaining crystal lattice sufficient to also influenc e the kinetics of chemical degradation. (C) 1997 Elsevier Science B.V.