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

Abstract

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 C_max 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.

Keywords: SNEDDS; Ticagrelor; in vivo bioavailability studies; myocardial infarction; solubility; thrombosis.