Versatile mixed micellar Pluronic formulations as drug delivery carriers for aripiprazole and carbamazepine - A comparative study

This research work focused on exploring the drug delivery systems for hydrophobic drugs viz. aripiprazole (APZ), and carbamazepine (CBZ) using mixed micelles (MMs) composed of shorter PEO (Poly-ethylene-oxide) region Pluronics (L121, L81, L64 and L61) and comparative longer PEO region Pluronic P84. Drug loading results revealed 4.05-fold increase in the solubility of APZ from 0.69 mg/mL (5% w/v L121) for pure Pluronic micelles to 2.8 mg/mL in MMs (3:2 L121-P84). In the case of CBZ, the loading was found to be 0.290 mg/mL (5% w/v L121) and 1.036 mg/mL (4:1 L121-P84), which is significantly lower as compared to APZ loading in these investigated pure and MMs. The increase in particle size after APZ loading from 83.56 nm (polydispersity index (PDI) =0.23) to 125.48 nm (PDI = 0.28) of 3:2 L121-P84 indicated successful encapsulation of drugs within MMs. Differential pulse voltammetry (DPV) demonstrated that APZ exhibited strong binding affinity for best performing 3:2 L121-P84 MMs with highest binding constant of 17.53 x 108 M- 1 . Fourier Transform Infrared Spectroscopy (FTIR) studies also confirmed the presence of hydrogen bonding between 3:2 L121-P84 MMs and APZ. In vitro studies in L121-P84 MMs indicated that APZ showed a sustained release within 84 hand followed zero order kinetics whereas CBZ showed less sustained release in 11 h and followed KP model. This research showed that Pluronic MMs with shorter and longer PEO regions can substantially improve the loading of hydrophobic drugs and due to versatility of Pluronics, these systems can be explored for variety of hydrophobic drugs.