Transdermal Delivery of Domperidone via Solid Dispersion: Formulation, Characterization, and Ex Vivo Permeation

Transdermal drug delivery systems (TDDS) provide various advantages, including avoiding hepatic first-pass metabolism, ensuring prolonged drug release, and improving patient compliance. Domperidone, a dopamine antagonist with limited oral bioavailability due to significant first-pass metabolism, makes an excellent candidate for transdermal application. Objective: Develop and test domperidone transdermal patches employing hydrophilic polymers like PVP K-30 and HPβCD to improve solubility and release. Methods: Methods: Domperidone SDs were formulated with PVP K-30 and HPβCD in various ratios (1:1, 1:3, 1:5 w/w). FTIR and DSC were carried out to check compatibility and crystallinity. Transdermal patches were prepared following a solvent casting method with polymers (EC, HPMC, PVP) and plasticizers (PEG, DBP). Physicochemical properties like drug content, moisture content, tack, and diffusion were determined. In vitro release of the drug was analyzed through Franz diffusion cells, and release kinetics was determined. Skin irritability was determined through PII scoring. Results: Domperidone's solubility rose dramatically (up to 4.75 times) with PVP K-30. The amorphous nature of SDs and successful complexation were verified by FTIR and DSC. When compared to pure drug patches, patches with SD (especially PVP K-30) demonstrated better drug release. Over eight hours, the cumulative release of the optimized patch (P6, 1:5 SD with 50% DBP) was 87±11.65%. Safety with PII < 2 was confirmed by skin irritation tests. Conclusion: Transdermal patches of domperidone based on a solid dispersion matrix greatly enhanced the drug's solubility, release rate, and skin compatibility. As a patient-friendly, sustained-release substitute for oral domperidone therapy, the optimized SD patch formulation shows promise.