Effect of temperature on the surface free energy and acid–base properties of Gabapentin and Pregabalin drugs − a comparative study

Abstract

The surface energetics of Gabapentin (GBP) [2-[1-(aminomethyl) cyclohexyl] acetic acid] and Pregabalin (PGB) [(S)-3-(aminomethyl)-5-methylhexanoic acid] were studied using a surface energy analyzer (SEA); a new-generation inverse gas chromatography technique, in the temperature range of 298.15–323.15 K. The Lifshitz–van der Waals dispersive (γ^d_s) component of the surface energy was calculated using Schultz and Dorris-Gray methods. The specific free energy of adsorption (ΔG^sp_a) and specific component of surface free energy (γ^sp_s) were determined using Schultz and Polarization methods. For both the drugs, the γ^d_s component of the surface energy was found to decrease with the increase in temperature. The γ^d_s component of the surface energy obtained for GBP and PGB surfaces suggested that GBP is slightly more energetically active than PGB. However, the PGB surface showed slightly higher γ^sp_s implying its more polar nature as compared to GBP. These drugs with different structures but identical functional groups (–NH₂ and –COOH), were found to have a higher surface Lewis base parameter, (K_b), indicating predominately basic surfaces. Furthermore, the temperature dependence of the Lewis acid–base parameters for these drugs was attributed to the disruption of intramolecular hydrogen bonding at higher temperatures.