# Preparation of Felodipine–PEG Solid Dispersions by Solvent-Free scCO2 Processing and Their Translation into Orally Disintegrating Tablets

## TL;DR

This study uses a green, solvent-free method to improve the solubility of felodipine, a poorly water-soluble drug, and successfully translates it into fast-dissolving tablets.

## Contribution

A solvent-free scCO2 method is developed to create high-performance solid dispersions of felodipine suitable for orally disintegrating tablets.

## Key findings

- PEG 4K and PEG 20K solid dispersions showed significantly enhanced dissolution compared to crystalline felodipine.
- PEG 20K-based ODTs had superior mechanical strength while maintaining rapid drug release.
- The scCO2 method effectively reduced felodipine crystallinity, improving its solubility and bioavailability.

## Abstract

Poor aqueous solubility remains a major limitation for
the oral bioavailability of molecules such as felodipine (FDP), necessitating
formulation strategies that enhance drug dissolution while remaining
compatible with scalable, solvent-free processing. In this study,
solid dispersions (SDs) of FDP were prepared using an organic solvent-free
supercritical carbon dioxide (scCO2) process with four
grades of polyethylene glycol (PEG 4K, 6K, 10K, and 20K) at drug loadings
of 10, 20, and 30% w/w. The influence of PEG molecular weight, drug
loading, and scCO2 processing conditions on the solid-state
properties and dissolution behavior of FDP was investigated. X-ray
diffraction (XRD) and differential scanning calorimetry (DSC) revealed
a substantial reduction in FDP crystallinity, indicative of partial
or extensive amorphization, dependent on polymer grade and processing
temperature. All SDs showed markedly enhanced dissolution compared
with crystalline FDP and corresponding physical mixtures, with PEG
4K SDs processed at 45 °C and PEG 20K SDs processed at 60 °C
exhibiting the most pronounced improvements. Optimized SDs were subsequently
incorporated into orally disintegrating tablets (ODTs), which retained
the enhanced dissolution performance of the parent SDs, demonstrating
that tabletting did not compromise drug release. While both PEG 4K-
and PEG 20K-based ODTs showed rapid dissolution, PEG 20K formulations
exhibited superior mechanical integrity, identifying 30% w/w drug-loaded
PEG 20K SDs as the most suitable system for ODT development. Overall,
this study demonstrates a green, solvent-free scCO2-based
strategy for producing high-performance solid dispersions and their
successful translation into ODTs for poorly water-soluble drugs.