Sertraline-Cyclodextrin Complex Orodispersible Sublingual Tablet: Optimization, Stability, and Pharmacokinetics

Abstract

Sertraline HCl (SRT) is a selective serotonin reuptake inhibitor (SSRI) that is used to treat depression and anxiety disorders. SRT is characterized by limited water solubility and suffers from low bioavailability due to first-pass effect. Therefore, this study aims to formulate SRT-Cyclodextrin (CD) orodispersible tablet (ODT) using direct compression technique to avoid SRT drawbacks. A 22 × 3 full factorial design was adopted using three factors, namely, CD type (βCD and HPβCD), SRT-CD mixing type (physical and solid dispersion), and type of diluent/superdisintegrant (xylitol/polyvinylpyrrolidone, maltitol/polyvinylpyrrolidone, and maltitol/co-processed mixture of polyvinylpyrrolidone and Ac-Di-Sol). Precompression studies were carried out on each formulation blend followed by the characterization of the prepared ODTs. All the ODTs were assessed for weight variation, hardness, friability, content uniformity, in vitro disintegration time, wetting time, water absorption ratio, in vitro dispersion time, and in vitro dissolution study. Accelerated and long-term stability studies were executed on the selected formulation. A pharmacokinetic study of the selected SRT ODT was accomplished through sublingual administration using LC/MS/MS assay in comparison to the conventional oral tablet Lustral®. ODT prepared with SRT-βCD solid dispersion with maltitol/polyvinylpyrrolidone (F4) led to reducing the disintegration time (9 ± 1.41 sec) and enhancing the dissolution efficiency (84 ± 2.5%). It showed a significant decrease of Tmax to 4 h instead of 8 h for Lustral® and increased the extent of drug absorption with a relative bioavailability of 117%. SRT orodispersible sublingual tablet can be considered as a promising delivery system for the treatment of depression. SRT sublingual ODT can avoid first-pass effect of SRT and hence improve its bioavailability due to the enhancement of SRT dissolution and rapid absorption through the oral mucosa.