# Development of long-acting riluzole transdermal patch against amyotrophic lateral sclerosis: Mechanistic insights into polyglyceryl-3 dioleate-enhanced drug release and skin permeation

## TL;DR

A long-acting transdermal patch for ALS treatment was developed, using polyglyceryl-3 dioleate to improve drug release and skin absorption.

## Contribution

The study introduces a novel transdermal patch formulation with polyglyceryl-3 dioleate to enhance riluzole delivery for ALS patients.

## Key findings

- The optimized patch formulation achieved a riluzole penetration rate of 2.96 μg/(h·cm²).
- Polyglyceryl-3 dioleate improved drug release and transdermal absorption by increasing skin lipid fluidity.
- The patch showed prolonged pharmacokinetic performance with no significant skin irritation.

## Abstract

Patients with amyotrophic lateral sclerosis (ALS) often experience difficulty swallowing, making oral administration unsuitable for effective treatment. A transdermal drug delivery system (TDDS) offers a long-acting, non-invasive alternative for ALS therapy. In this study, a riluzole transdermal patch capable of sustained release over 72 h was developed. In vitro skin permeation and pharmacokinetic experiments were conducted to evaluate the impact of various factors—including drug loading, type and concentration of chemical penetration enhancers (CPEs), and type of pressure-sensitive adhesive—on riluzole absorption through the skin. The optimized patch formulation contained 17 % (w/w) riluzole and 10 % (w/w) polyglyceryl-3 dioleate (PGD), with an adhesive layer thickness of 111 μm. The final prescription penetration rate of riluzole was found to be 2.96 μg/(h·cm2). Optimized formulation displayed enhanced stability and prolonged pharmacokinetic performance (Cmax = 74.34 ± 13.62 ng/mL, MRT0-t = 34.91 ± 11.31 h). No significant skin irritation was observed. The role of PGD in the in vitro release and in vivo transdermal absorption of riluzole was thoroughly investigated. The results revealed that PGD not only reduced the interaction between riluzole and the pressure-sensitive adhesive, enhancing drug release but also increased the fluidity of skin lipids, leading to improved transdermal absorption. This study provides a comprehensive molecular-level understanding of PGD's effect on riluzole permeation, offering valuable insights for the rational selection of CPEs in the development of riluzole TDDS.

Unlabelled Image

•A novel long-acting riluzole transdermal patch was developed.•Polyglyceryl-3 dioleate enhanced riluzole release from transdermal patch.•Polyglyceryl-3 dioleate increased the fluidity of skin lipids.

A novel long-acting riluzole transdermal patch was developed.

Polyglyceryl-3 dioleate enhanced riluzole release from transdermal patch.

Polyglyceryl-3 dioleate increased the fluidity of skin lipids.