Formulation and Evaluation of Ticagrelor Nanosuspension Loaded Fast Dissolving Sublingual Films

Background: To address the solubility challenges of Ticagrelor, a poorly water-soluble drug, and improve its absorption and permeability, this study explores innovative drug delivery technologies. Specifically, the development of a nanosuspension formulation is investigated as a means to enhance Ticagrelor's solubility and, consequently, its bioavailability. Additionally, the study considers the incorporation of this nanosuspension into a sublingual fast dissolving film, which can further improve the drug's therapeutic efficacy by enabling rapid onset of action and bypassing first-pass metabolism. This dual approach aims to maximize the clinical benefits of Ticagrelor by leveraging advanced formulation techniques. Method: A nanosuspension of Ticagrelor was prepared using the antisolvent precipitation technique. This nanosuspension was then employed to develop nanosuspension-loaded sublingual fast-dissolving films (NSP-FDFs) through solvent casting, guided by a 3² factorial design. Key evaluation parameters included particle size, zeta potential, entrapment efficiency, as well as various physical properties of the NSP-FDFs, such as thickness, weight uniformity, disintegration time, and tensile strength. Results: The optimized TCG-NSP batch N6 showed a significant improvement in solubility. Evaluation metrics highlighted the nanosuspension's effectiveness, with a desirable particle size of 190 nm, a zeta potential of -24.6 mV, and a high encapsulation efficiency of 92.44±0.78%. Solubility studies revealed values of 1.911 mg/ml in distilled water and 2.981 mg/ml in salivary fluid, while TEM imaging confirmed the internal structure of the optimized batch. Furthermore, the optimized batch F9 for nanosuspension-loaded sublingual fast-dissolving films (NSP-FDFs) exhibited ideal characteristics, including a thickness of 0.294±0.082 mm, a tensile strength of 10.87±0.34, a rapid disintegration time of 63.31±1.58 seconds, an in vitro drug release of 92.60±0.05%, and a permeability of 91.04±0.06%. These properties ensure efficient drug delivery and a quick onset of action. Conclusion: The study successfully developed a TCG-NSP and incorporated it into Nanosuspension loaded sublingual fast-dissolving films. These films demonstrated improved solubility and may increase bioavailability, positioning them as a promising option for effective Ticagrelor delivery. The findings suggest that this approach could also be beneficial for enhancing the delivery of other poorly soluble medications.