Evolution of non-covalent derivatives of pioglitazone with salicylic acid and its impact on crystallite characteristics and dissolution

The bioavailability of a molecule is considerably influenced by its crystalline nature and behaviour, depending on various factors such as internal structure within its crystal lattice. This study aims to develop pioglitazone (PIO) eutectics with co-former salicylic acid (SA). And its effect on crystallite properties as well as drug dissolution has been studied. Pioglitazone-salicylic acid eutectic formulations i.e., PS1, PS2, and PS3 using different molar ratios of 1:1, 2:1, and 1:2 respectively were prepared using the ethanolic solvent evaporation method. DSC study showed a broad peak at 117.696 °C, which is lower than the melting peaks of PIO (195.61°C) as well as SA (158.69°C) confirming the formation of eutectic. Carbonyl-thiazolidine non-covalent bond or pi-pi attraction might have been involved for the formation of eutectics of PIO-SA having the docking score of -2.5 Kcal/M rather than co-crystals. Having a maximum value of strain (12.69 ± 8.04) in PS2 possibly due to higher deformity within the molecular layer when compared to other formulations and raw PIO. Further, the crystallite size of PS2 (18.57 ± 9.91 nm) was found to be smaller than the others (32.19 to 70.77 nm). All eutectic formulations presented improvement in drug dissolution. PS2 (PIO-SA as 2:1 molar ratio) resulted in drug release more quickly (86.90 %) than pure PIO (44.50 %) and other formulations (62.76 to 72.15 %) at 5 h. Consequently, creating eutectic formulations may be a useful tactic for enhancing PIO solubility.