Changsha Jingyi Pharmaceutical Technology Co., Ltd

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. 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.

Orodispersible films (ODFs), easy to administer, flexible in dosage, and free of choking and aspiration risks, have drawn widespread attention as pediatric formulations. However, it is a great challenge to endow ODFs with sustained release due to their fast disintegration. Herein, we designed a novel orodispersible film load with dual-coated sustained-release microparticles (SRMPs) for children using topiramate as a model drug. SRMPs with a particle size of 98.32 ± 0.22 µm, fabricated with a pellet core, a drug layer, and a coating layer, were prepared by two microparticle coating steps. The sustained-release orodispersible films (SRODFs) with uniform distribution of SRMPs and favorable disintegration time showed good formability, mechanical properties, and palatability. The factors affecting drug release of the SRMPs and the SRODFs were further explored. More importantly, pharmacokinetics study in human demonstrated that, although the SRODFs had a longer mean retention time, they were bioequivalence compared with the commercially available extended-release products (Qudexy® XR). A strong in vivo-in vitro correlation of the SRODFs was established. Notably, the SRODFs can be loaded with other drugs other than topiramate, offering a promising formulation option for pediatric patients with different diseases.

Dapoxetine hydrochloride tablets are the most commonly used drug for the treatment of premature ejaculation (PE). However, the tablets must be taken with water 1-3 h before sexual activity, which makes the medication intake conspicuous and inconvenient. This study aimed to develop taste-masked orodispersible films (ODFs) of dapoxetine hydrochloride using ion exchange resins. It was found that the based-Kyron T-134 resin complex achieved a high drug loading of 75.9 ± 1.4%, establishing the mass ratio of dapoxetine hydrochloride to Kyron T-134 at 2:1, and adjusting the solution pH to 5.4 ± 0.05. The effect of pH on the drug loading of the resin was initially characterized by SEM, while the binding mechanism between dapoxetine hydrochloride and the resin was investigated by XRD, DSC, and FTIR. The ODFs exhibited favorable mechanical properties and palatability. Meanwhile, the drug release in both the ODFs and commercially available tablets Priligy^® could reach 100.8% of the drug over 15 min in a simulated gastric fluid with pH 1.2 HCl. Furthermore, pharmacokinetic studies conducted in healthy volunteers demonstrated that the ODFs were bioequivalent to Priligy^®. Therefore, this ODFs, characterized by its pleasant taste and water-free administration, offer a novel and convenient oral formulation for patients with PE, thereby enhancing patient compliance.