Formulation and In Vivo Evaluation of Ticagrelor Self-nanoemulsifying Drug Delivery Systems.

BACKGROUND: Ticagrelor (TGR), being an antiplatelet agent, belongs to BCS class IV drug with low solubility and permeability that undergoes first-pass metabolism, leading to reduced bioavailability of 36%. OBJECTIVE: The main objective of this study is to develop TGR SNEDDS for enhancing solubility and oral bioavailability. METHODS: An oil, surfactant and co-surfactant (miglyol 810, brij 35 and lauro glycol FCC) are chosen based on the maximum solubility of TGR. The selected vehicles are mixed in different ratios and are agitated mildly. Transmittance values that are more than 80 were noted and are used for constructing pseudo ternary phase diagram. Formulations that passed stability testing were evaluated for % transmission, drug content and in vitro drug release analysis. In vivo bioavailability studies of optimized SNEDDS are performed in Wistar rats. RESULTS: From evaluation studies of TGR, formulation F13 with maximum drug release of 98.99% in 60 minutes, that is higher than 31.99% of the pure drug is considered as an optimised formulation. The particle size, Z average and zeta potential of the optimized TGR formulation F13 was 289.6 nm, 185.1 nm and -18.3 mV respectively. The FTIR and SEM studies do not indicate any drug excipient interaction and confirm nano size which is stable for 3 months. From in vivo bioavailability studies in rats, the Cmax of optimized TGR SNEDDS (302.43±4.78 ng/ml) is higher than pure TGR suspension (47.32±2.75 ng/ml) and optimized SNEDDS exhibited 5 folds increase in oral bioavailability when compared to pure drug. CONCLUSION: Hence the results reveal that, application of SNEDDS formulation technique for TGR Increases solubility and oral bioavailability.

Self Nanoemulsifying Drug Delivery System of Sorafenib Tosylate: Development and In Vivo Studies.

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.