Transdermal microneedle delivery of rivaroxaban and its inclusion complex for enhanced anticoagulant therapy

Rivaroxaban (RIV), an oxazolidinone derivative, is an oral anticoagulant used in the prevention and treatment of arterial and venous thromboembolic conditions. However, its oral administration is limited by its poor solubility and bioavailability. The current study aims to load this drug (RIV) into novel transdermal microneedle patches (MNPs) and assess the solubility-enhanced RIV inclusion complex (RIV-IC) as an alternative delivery approach. Scanning electron microscopy (SEM) confirms the presence of uniform, sharply tipped microneedles with a smooth morphology, and differential scanning calorimetry (DSC) indicates good drug-polymer compatibility. The permeation capabilities were analysed using a Franz diffusion cell across rat skin, which demonstrated efficient skin penetration and drug release (∼85% for RIV and ∼94% for RIV-IC within 90 minutes). Insertion capacity was confirmed using Parafilm and rat skin. In vivo pharmacodynamic studies in rats showed significant anticoagulant activity. Histological studies also demonstrated successful microneedle insertion through the stratum corneum without vasculature damage. Overall, these findings indicate that the RIV- and RIV-IC-loaded microneedle patches represent a promising transdermal drug delivery system with enhanced therapeutic efficacy and serve as a viable alternative to oral anticoagulants for the management of thromboembolic disorders.