Pamu Sandhya*, Pamu Poornima and Darna V.R.N. Bhikshapathi Pages 471 - 484 ( 14 )
Background: Sorafenib tosylate (SFN) belongs to the BCS class II drug with low solubility and undergoes first-pass metabolism, which leads to reduced bioavailability of 38%.
Objective: The present study aimed at developing SFN SNEDDS to improve their solubility and bioavailability.
Methods: Preliminary solubility studies were performed to identify oil, surfactant, and co-surfactant ratios. Pseudo tertiary phase diagram was constructed to select the areas of nanoemulsion based on the monophasic region. A total of 15 formulations of SFN SNEDDS were prepared and screened for phase separation and temperature variation using thermodynamic stability studies. These SNEDDS further characterized for % transmission, content of the drug, and in vitro dissolution analysis. The optimized formulation was analyzed for particle size, Z average, entrapment efficiency, and SEM analysis.
Results: Based on the pseudo tertiary phase diagram, acrysol EL 135, kolliphor, and transcutol-P as oil, surfactant, and co-surfactant were selected, respectively. All the formulations were stable with no phase separation and maximum % transmittance of 98.92%. The formulation F15 was selected as an optimized one, based on maximum drug content of 99.89%, with 98.94% drug release within 1 hour and it will be stable for 6 months. From in vivo bioavailability studies, the Cmax of optimized SNEDDS (94.12±2.12ng/ml) is higher than pure SFN suspension (15.32±1.46 ng/ml) and the AUC0-∞ of optimized SNEDDS is also increased by 5 times (512.1±8.54 ng.h/ml) than pure drug (98.75±6.45ng.h/ml), which indicates improved bioavailability of the formulation.
Conclusion: SFN loaded SNEDDS could potentially be exploited as a delivery system for improving oral bioavailability by minimizing first-pass metabolism and increased solubility.
Lay Summary: Renal cell carcinoma accounts for 2% of global cancer diagnoses and deaths, it has more than doubled in incidence in the developed world over the past half-century, and today is the ninth most common neoplasm in the United States. Sorafenib is a protein kinase inhibitor indicated as a treatment for advanced renal cell carcinoma. The present study aimed at developing Sorafenib SNEDDS to improve their solubility and bioavailability. A total of 15 formulations of Sorafenib SNEDDS were prepared and screened for phase separation and temperature variation using thermodynamic stability studies. Sorafenib loaded SNEDDS could potentially be exploited as a delivery system for increased oral bioavailability by 5 times when comparing with pure drug by minimizing first-pass metabolism and increased solubility.
Bioavailability studies, pseudoternary phase diagram, SNEDDS, solubility, sorafenib tosylate, acrysol EL 135.
Department of Pharmaceutics, Shadan Women’s College of Pharmacy, Hyderabad, Telangana, Department of Pharmaceutics, Mallareddy Pharmacy College, Secunderabad, Telangana, Department of Pharmaceutics, Teegala Ram Reddy College of Pharmacy, Hyderabad, Telangana