Abstract

Levothyroxine (LT4) is used to treat hypothyroidism. However, it presents challenges relating to bioavailability, absorption, and patient adherence when administered as a conventional tablet. This study aimed to enhance LT4 delivery using fast-dissolving films (FDFs) and fast-dissolving tablets (FDTs). These formulations incorporate nanocarriers to potentially enhance LT4 buccal delivery and absorption. Liposomes containing LT4 were prepared using a microfluidic system. All liposome formulations were prepared at a target concentration of 100 μg/mL. Each formulation contained Tween® 80, cholesterol, and phospholipid. Niosomes were formulated using Span® 60 and cholesterol. They were then optimised using Tween® 80 and charge inducers (DOTAB and stearic acid) under the same conditions. Nanocarriers were characterised for Z-average, defined as the intensity-weighted mean hydrodynamic particle diameter; polydispersity index (PDI), which describes the breadth of the particle-size distribution; and encapsulation efficiency (EE%). The optimised formulations were incorporated into FDFs using solvent casting and into FDTs using lyophilisation and direct compression. In vitro dissolution studies were performed using USP Apparatus II (paddle) at 75 rpm in 500 mL of phosphate buffer (pH 7.4) at 37 ± 0.5 °C, with 5 mL samples collected at 1, 3, 5, 10, 15, 30, 45 and 60 min. DSPC-based liposomes demonstrated the highest EE of 85.90%. The DSPC liposomes also demonstrated a Z-average of 153.2 nm and PDI of 0.184. The optimised niosome system (Span® 60 40%, cholesterol 45%, Tween® 80 10%, and DOTAB 5%) had a higher EE of 91.88%, with a Z-average of 218.47 nm and PDI of 0.094. Liposome-loaded FDFs demonstrated rapid disintegration (16 s) and folding endurance of >300 folds, while niosome-loaded FDFs showed a mean weight of 200.7 mg, a thickness of 0.289 mm and rapid disintegration (40 s). Lyophilised FDTs exhibited greater porosity and faster disintegration than directly compressed tablets. The incorporation of LT4-containing liposomes and niosomes into FDFs and FDTs resulted in rapid LT4 release during the in vitro dissolution study. In conclusion, the data suggest that nanocarrier-integrated FDF and FDT systems show potential as oromucosal delivery platforms for LT4 and warrant further ex vivo permeability and in vivo evaluation.