# Design of Experiment Approach for Enhancing the Dissolution Profile and Robustness of Loratadine Tablet Using D-α-Tocopheryl Polyethylene Glycol 1000 Succinate

## TL;DR

This study uses a design-of-experiment approach to improve the solubility and effectiveness of loratadine tablets by optimizing the use of TPGS and SSG.

## Contribution

The novel use of TPGS in wet granulation to enhance dissolution and robustness of a BCS II drug is presented.

## Key findings

- TPGS and SSG significantly improved granule and tablet properties, with TPGS having a notable effect.
- Optimized concentrations of 5.0% TPGS and 2.0% SSG produced tablets with good mechanical strength and dissolution.
- The optimized formulation showed a dissolution rate of 86.21% and disintegration time of 7.11 minutes.

## Abstract

Background: Formulating poorly water-soluble drugs poses significant challenges due to their limited solubility and bioavailability. Loratadine (LTD), classified as a BCS II molecule, exhibits notably low solubility, leading to reduced bioavailability. Objective: This study aims to enhance the dissolution rate of LTD through the utilization of the wet granulation process using Tocopheryl polyethylene glycol 1000 succinate (TPGS). Methods: A Design-of-Experiment methodology was adopted to investigate and optimize the formulation variables for preparing an oral delivery system of LTD with improved dissolution properties. The levels of TPGS (2–6% w/w), as a surfactant, and sodium starch glycolate (SSG; 2–8% w/w), as a super-disintegrant, were established as independent variables in the formulations. Loratadine was granulated in the presence of TPGS, and the resultant granules were subsequently compressed into tablets. The granules and tablets produced were then subjected to characterization. Results: ANOVA analysis indicated that both TPGS and SSG had a significant (p < 0.05) influence on the critical characteristics of the obtained granules and tablets, with TPGS showing a particularly notable effect. The optimal concentrations of TPGS and SSG for the development of LTD tablets with the necessary quality attributes were identified as 5.0% w/w and 2.0% w/w, respectively, through optimization utilizing the desirability function. The tablets produced at these optimized concentrations displayed favorable properties concerning their mechanical strength (5.72 ± 0.32 KP), disintegration time (7.11 ± 1.08 min.), and release profile (86.21 ± 1.61%). Conclusions: In conclusion, incorporating TPGS in the granulation process shows promise in improving the dissolution profile of poorly water-soluble drugs and demonstrated formulation robustness.