Development of long-acting imidafenacin transdermal patches with high drug loading based on solid dispersion technology

Abstract

Imidafenacin tablets are the first-line drug for the treatment of overactive bladder (OAB). However, the tablets need to be taken twice daily for up to 3–6 months, which highly reduces patient compliance. This study aimed to develop a long-acting imidafenacin transdermal patch (LAITP) with high drug loading using amorphous solid dispersion technology (ASD). ASD, consisting of polyvinyl pyrrolidone and imidafenacin, not only significantly increased the drug loading in the patch, but also inhibited drug crystallization.

Highlights

Molecular weight of PVP was the key to the formation of ASD.

ASD could increase the drug loading and inhibited crystallization in the patch.

The formation mechanism of ASD was systematically elucidated.

The LAITP was optimized by ternary phase diagram analysis.

The LAITP prolonged sustained effective plasma concentration in human.

Furthermore, the formation mechanism of ASD was systematically elucidated using SEM, XRD, DSC, FT-IR, and molecular docking. The LAITP was optimized through single-factor investigations and ternary phase diagram analysis. It was confirmed by SEM and confocal Raman microscopy that ASD was a spherical microparticle with a size of 28.62 ± 8.91 µm in LAITP. Notably, under long-term and accelerated conditions of 3 months, the LAITP exhibited excellent stability to ensure the reliability of quality.

Importantly, human pharmacokinetic studies demonstrated that LAITP with low skin irritation and favorable adhesion properties prolonged sustained effective plasma concentration in comparison to commercial tablets (Staybla®), reducing the frequency of administration and thereby improving patient compliance, which is expected to be a promising treatment option for patients with OAB.

Materials

IMI was purchased from Beijing Hope Pharmaceutical Co., Ltd. (Beijing, China). Staybla® was purchased from Ono Pharmaceutical Co., Ltd. (Osaka, Japan). Pressure sensitive adhesive (PSA, DURO-TAK® 87–4098) was purchased from Henkel Co. (Dusseldorf, Germany). ScotchpakTM 9709 release film and CotranTM 9720 backing films were purchased from 3 M Co. (St. Paul, USA). Polyvinyl pyrrolidone (PVP) K12, K30, and K90 were gifted by Yunhong Excipients, Co., Ltd. (Shanghai, China).

Jianing Lin, Peng Yan, Hailong Zhang, Jinsong Ding, Development of long-acting imidafenacin transdermal patches with high drug loading based on solid dispersion technology, International Journal of Pharmaceutics, Volume 679, 2025, 125741, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2025.125741.