The Development and Optimization of Hot-Melt Extruded Amorphous Solid Dispersions Containing Rivaroxaban in...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Materials Science

Background:

• Rivaroxaban (RXB) is a Biopharmaceutics Classification System (BCS) class II drug, characterized by poor solubility and low oral bioavailability.
• Direct oral anticoagulants like RXB require effective formulation strategies to enhance therapeutic efficacy.

Purpose of the Study:

• To develop and optimize a hot-melt extruded amorphous solid dispersion (HME-ASD) of rivaroxaban (RXB) for improved oral drug delivery.
• To evaluate the impact of formulation parameters on the solubility, dissolution, and bioavailability of RXB-ASD.
• To assess the stability and pharmacokinetic profile of the optimized RXB-ASD formulation.

Main Methods:

• Preparation of RXB-ASD using hot-melt extrusion (HME) with varying drug:polymer ratios and barrel temperatures.
• Optimization of the HME-ASD formulation using a central composite design (CCD).
• In vitro dissolution studies in multiple media, accelerated stability testing, and pharmacokinetic studies in rats.

Main Results:

• The optimized RXB-ASD formulation (PVP VA 64 ratio 1:4.1, barrel temperature 216.1 °C) demonstrated high dissolution rates, achieving ~80% cumulative drug release within 120 minutes.
• The optimized RXB-ASD remained stable for three months under accelerated conditions, showing no changes in crystallinity or dissolution.
• Pharmacokinetic studies in rats revealed significantly increased absorption rate and extent (systemic exposure) of RXB from the optimized RXB-ASD compared to raw RXB powder.

Conclusions:

• Hot-melt extrusion is an effective technique for preparing stable rivaroxaban amorphous solid dispersions (RXB-ASD) with enhanced dissolution and bioavailability.
• The application of Quality by Design (QbD) principles facilitated the optimization of RXB-ASD formulation for improved oral drug delivery.
• The developed RXB-ASD holds significant potential as an advanced oral dosage form for rivaroxaban therapy.