Formulation And Biopharmaceutical Evaluation Of Ticagrelor Loaded Pegylated Solid Lipid Nanoparticles Using Quality By Design

Abstract

Ticagrelor (TGL) is an antiplatelet agent classified under BCS class IV, known for its limited oral bioavailability of 36%. This research aims to develop an optimized formulation of Solid Lipid Nanoparticles (SLNs) employing central composite design to enhance the solubility and permeability of Ticagrelor. The preparation of Pegylated Solid Lipid Nanoparticles (PSLNs) involves utilizing the hot homogenization method with GMS, Poloxamer 407, and Tween 80. Three independent variables, namely lipid to drug ratio (X1), surfactant concentration (X2), and PEG 2000 amount (X3), are considered, while particle size, Zeta potential, percent Encapsulation Efficiency (%EE), and Polydispersity Index (PDI) serve as the dependent variables. The optimized PSLNs undergo thorough characterization, including in-vitro, ex-vivo, DSC, SEM, and TEM analyses. Initial trial runs are conducted to select suitable ranges for optimization. The experimental design encompasses 16 runs, with particle size ranging from 323nm to 648nm, Zeta potential ranging from -21.45mV to -37.63mV, %EE varying between 83.28% and 92.00%, and PDI values ranging from 0.42 to 0.52. The formulation that emerges as the optimized one, exhibiting a probability of 0.548, demonstrates a particle size of 468.9nm, a Zeta potential of -29.37mV, % EE of 88.87%, and PDI of 0.36. The in-vitro release profile of the optimized formulation shows sustained drug release over 48 hours, with an impressive 93.42% drug release. The release mechanism follows non-Fickian diffusion, as evident from the n value of 0.9541. Moreover, the ex-vivo evaluation reveals a steady-state flux of 0.0096mg/cm² min. Furthermore, SEM and TEM studies confirm the successful Pegylation of the formulation, and they illustrate the effective encapsulation of the drug within the PSLNs. This research represents a promising step toward enhancing the solubility and permeability of Ticagrelor, offering potential improvements in its therapeutic efficacy and clinical outcomes. Keywords: Ticagrelor, Bioavailabi