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

This 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 was to evaluate activation energy (E_A) 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 E_A, providing an overall thermodynamic view on the studied glyceryl behenate matrix tablets, were 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 containing 10% to 50% of glyceryl behenate were prepared by the direct compression method. The tablets were of a cylindrical shape without facets with a diameter of 13 mm and a weight of 0.5 ± 0.0010 g. Dissolution testing was carried out according to the European Pharmacopoeia 9th using dissolution apparatus SOTAX AT7 Smart in an aqueous solution of HCl with addition of NaCl (pH1.2). The released amount of the model drug was determinated by UV/VIS spectroscopy.

Positive values of ΔH in the range of 3.83 to 56.13 kJ mol^–1 and positive values of ΔGindicate 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 was 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. Continue reading here