A New Approach to the Dissolution Tests Management to Obtain Kinetic and Thermodynamic Data: Release of a Model Drug from Glyceryl Behenate Matrix Tablets

Abstract

AbstractThis study is focused on the use of glyceryl behenate as a lipophilic excipient of matrix tablets providing controlled drug release. The aim of this study is to evaluate activation energy (EA) and changes of the thermodynamic parameters (ΔH, ΔS, ΔG) of a dissolution process. These values, which have not yet been published, can lead to better understanding of a drug release mechanism and can extend the use options of glyceryl behenate in the pharmaceutical industry. Values of ΔH, ΔS, ΔG and EA, providing an overall thermodynamic view on the studied matrix tablets, are evaluated based on the temperature‐dependences of the release rate constant of a model drug (temperature range 25 ‐ 45 °C). The studied lipophilic matrix tablets contain 10% to 50% of glyceryl behenate. Dissolution testing is carried out in an aqueous solution of HCl with addition of NaCl (pH1.2). Positive values of ΔH in the range of 3.83 to 56.13 kJ mol‐1 and positive values of ΔG indicate that the dissolution of the studied glyceryl behenate matrix tablets is an endothermic process which does not proceed spontaneously (in a temperature range of 25 ‐ 45 °C). The negative slope of the linear curves of enthalpy‐entropy compensation confirms the entropy‐driven dissolution.Practical Applications: A better understanding of the dissolution process is an important aspect, e.g., in the field of drug formulation strategy. In this study, it is confirmed that the influence of temperature on the model drug release rate is negligible for tablets containing more than 40% of glyceryl behenate. It is an important result for drug design due to the reduction of risk of a possible dose dumping effect induced by temperature and the prevention of in vivo therapeutic failure.