Advanced Oral Formulation of Atorvastatin and Fenofibrate: Solubility Enhancement and Bioavailability Optimization using Nanosuspension

The study aims to enhance the oral bioavailability and solubility of Atorvastatin, and Fenofibrate classified as a class (II) based on the Biopharmaceutical Classification System (BCS) used for treating hypertension. Hence, a combination nano suspension was developed using a high-speed homogenization. The selection of stabilizers was initially done using a One-Factor-At-A-Time method, considering particle size and potential. A Box-Behnken design with 3 factors and 3 levels was employed in 15 experimental trials to study how stabilizer concentration, homogenization speed and homogenization duration is impacting Zeta potential, Poly dispersity Index and Particle size. The combination of Poloxamer 407 and Polyvinylpyrrolidone were identified as the optimal stabilizer mix. The resulting nano suspension displayed a reduced particle size of 183.9nm and a zeta potential of -22.9mV. SEM images showed that the particles were spherical in shape. Further investigation with FT-IR, DSC, and X-ray diffraction studies substantiated the compatibility between the drugs and stabilizers used. The optimal formulation was used and yielded an expected solubility of the drug of 91.26±8.24μg/mL and 74.32±9.11 with the combination stabilizer with more than 90% drug release within the first hour. The formulation also showed C_max (2.97-fold) and AUC0-24h(2.49-fold) for Atorvastatin nano formulation, while for FNF nano formulation an increase in the value of C_max (3.74-fold) and AUC0-24h (3.17-fold) was evident, highlighting the effectiveness of the nano suspension in improving solubility, absorption, and bioavailability due to lesser particle size with a higher effective surface area that may facilitate solubility and possibly improve release.