Temperature-Dependent Solubilization of the Hydrophobic Antiepileptic Drug Lamotrigine in Different Pluronic Micelles-A Spectroscopic, Heat Transfer Method, Small-Angle Neutron Scattering, Dynamic Light Scattering, and in Vitro Release Study

Pluronics (tri-block copolymers) have a significant role in the pharmaceutical industry and are being used to enhance the solubility and delivery of hydrophobic drugs in different marketed formulations. However, instability and unsatisfactory drug-loading capacity are the major weak spots of these pluronic micelles. The present research work is designed to solve the existing issues by the solubilization study of hydrophobic drugs in different pluronic micelles at variable temperatures. The solubilization of the hydrophobic antiepileptic drug lamotrigine (LAM) in five different pluronic micelles viz. P84, P85, F127, F108, and F68 was studied at different temperatures, 37, 47, and 57 °C, using UV-visible spectroscopy. The solubilization of LAM in pluronic micelles increased with the increase in temperature. Small-angle neutron scattering (SANS) measurements were used to observe the morphological and structural changes taking place in pluronics by increasing the temperature. The SANS results showed the morphological changes of spherical P84 micelles to prolate ellipsoidal micelles at 57 °C due to remarkable increase in the aggregation number. This morphological conversion was further confirmed by the heat transfer method (HTM) and dynamic light scattering (DLS) measurements. DLS measurements confirmed that LAM-loaded micelles showed a greater hydrodynamic diameter (D _h) compared to unloaded micelles, assuring LAM solubilization in the pluronic micelles. The rate of controlled release of LAM from five different pluronic micelles was accessed by using different kinetic models to evaluate the in vitro release profile. This is the first report in which HTM measurements are established for the analysis of morphological changes in the thermoresponsive pluronic micelles in real time. The present work corroborates how we can control the drug-loading capacity, morphological structure of the drug carrier, as well as drug release by simply changing the temperature of pluronic micellar media.