First promising non-stimulant (guanfacine) transdermal patch for long-acting treatment of ADHD by solid dispersion technique

Guanfacine (GFC) extended-release tablet (Intuniv®) is an effective non-stimulant medication prescribed for attention deficit hyperactivity disorder (ADHD), presenting limitations regarding patient compliance and safety risks. The study aimed to design a novel long-acting transdermal delivery system of GFC to address these issues. Polyvinylpyrrolidone (PVP)-GFC solid dispersions were constructed by the co-evaporation method to improve drug-loading capacity to approximately 10 % (w/w). A PVP-GFC ratio of 3:1 was determined to prevent drug crystallization and promote rapid dissolution. The mechanisms underlying solid dispersion formation were revealed by XRD, DSC, molecular docking, FTIR, and Raman imaging.

Highlights

An innovative promising guanfacine transdermal patch was designed for ADHD therapy.

Desired drug-loading and release rate was achieved via solid dispersion techniques.

The mechanism underlying solid dispersion formation was comprehensively revealed.

Optimized patches exhibited significant potential for long-acting effects in humans.

Hydrogen-bond interactions between PVP and GFC played a crucial role. The prescription and preparation process were optimized using single-factor and Box-Behnken design experiments. The optimized patch exhibited excellent crystallization resistance and adhesion for at least six months. Additionally, superior rheology, mechanical strength, in vitro drug release, and percutaneous permeation characteristics were observed. In human pharmacokinetic studies, the therapeutic efficacy, skin safety, and adhesion of transdermal patches were initially demonstrated for the three-day treatment of ADHD. Therefore, the innovative work expands the comprehension of solid dispersion techniques and facilitates the industrialization and commercialization of the first non-stimulant transdermal patches, providing a promising alternative for ADHD therapy.

Materials

GFC was synthesized in the laboratory (purity >99.9 %). PVP K90 was gifted by Yunhong Excipients (Shanghai, China). DURO-TAK® 87–4098 PSA and DURO-TAK® 87–900A PSA were purchased from Henkel (Düsseldorf, Germany). Diethylene glycol monoethyl ether (Transcutol®, TC) was obtained from Gattefossé (Saint-Priest, France). Isopropyl myristate (IPM) and 1, 2-propanediol (PG) were from Jiudian Hongyang Pharmaceutical (Changsha, China). Oleyl alcohol (OA) and propylene glycol monolaurate (PGML).

Zhiyuan Hou, Xiangcheng Zhao, Jinsong Ding, First promising non-stimulant (guanfacine) transdermal patch for long-acting treatment of ADHD by solid dispersion technique, Journal of Drug Delivery Science and Technology, Volume 100, 2024, 106117, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2024.106117.