Design of Experiments (DoE)-Based Optimization of Pomalidomide Nanosuspension for Improved Oral Absorption and Pharmacokinetics

Abstract

Aim: The study aims to enhance the oral bioavailability and solubility of Pomalidomide (POM), which is classified as a class IV medication based on the Biopharmaceutical Classification System (BCS).Materials and Methods: A POM Nanosuspension (NS) was developed using a high-pressure homogenizer. The selection of stabilizers was initially done using a One-Factor-at-A-Time (OFAT) method, considering both PdI and Particle Size (PS). A Box-Behnken Design (BBD) with 3 factors and 3 levels was employed in 17 experimental trials to study how stabilizer concentration, cycle count, and pressure impact Zeta Potential (ZP) and PS. The combination of Soluplus® and Hydroxypropyl Methylcellulose (HPMC) was identified as the optimal stabilizer mix.Results: The resulting NS displayed a reduced PS of 132.9 nm and a ZP of -22.9 mV. SEM images showed that the particles were spherical. Further investigation with FT-IR, DSC, and X-ray Diffraction (XRD) studies substantiated the compatibility and alteration of POM into an amorphous state. The optimized POM-NS demonstrated a 21.56-fold increase in solubility, with more than 97% drug release within the first hour. The formulation also showed a 2.14-fold increase in Cmax and a 1.56-fold increase in AUC0-t.Conclusion: The modified POM NS markedly improved solubility, oral absorption, and bioavailability, indicating its potential for higher therapeutic efficacy.

Keywords: Pomalidomide; Nanosuspension; Box-Behnken; Design; Drug; Release; Pharmacokinetics