Kinetic study of the Maillard reaction between metoclopramide hydrochloride and lactose.
The purpose of this work is to study the apparent solid-state kinetics of the Maillard reaction of the colyophilized metoclopramide hydrochloride (MCP) and lactose system and to elucidate some of the effects of molecular mobility on the kinetic behavior of the amorphous mixture. Colyophilized MCP-lactose mixtures (1:9 molar ratio) were stored at temperatures ranging from 100 to 115 degrees C (above the glass transition temperature, Tg=99.7 degrees C). This temperature range, which corresponds to the change between the glass and liquid states of the lactose-MCP mixtures, is also the temperature region where molecular mobility represents a kinetic impediment of enough significance as to affect the observed order of the reaction. A pseudo second-order kinetic model was developed to fit the MCP loss data. The proposed model gives better fit to the degradation data than many of the commonly used kinetic models available in the literature. The second-order rate constant of the model follows Arrhenius kinetics and the activation energy was found to be 53.8 kcal mol(-1). The molecular mobility (relaxation time) of the mixture was calculated from the heating rate dependence of the DSC-determined glass transition temperature of the mixtures. From molecular mobility considerations alone, it is possible to accurately predict the temperature dependence of the reaction rate constant. These results support the hypothesis that the solid-state reaction is mobility controlled.
Qiu
Zhihui
Z
Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907-1336, USA.
Stowell
Joseph G
JG
Morris
Kenneth R
KR
Byrn
Stephen R
SR
Pinal
Rodolfo
R
D005612:Freeze Drying; D007700:Kinetics; D007785:Lactose / Q000737:chemistry*; D015416:Maillard Reaction; D008787:Metoclopramide / Q000737:chemistry*; D008956:Models, Chemical; D013696:Temperature
D007785:Lactose; D008787:Metoclopramide