Enhanced Oral Bioavailability of Felodipine via Solid Self-microemulsion Delivery System

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Pharmacokinetics

Background:

• Felodipine (FEL) is a first-line antihypertensive drug with low oral bioavailability.
• Poor aqueous solubility and first-pass metabolism limit FEL's therapeutic efficacy.
• Enhancing FEL oral bioavailability is crucial for effective hypertension management.

Purpose of the Study:

• To develop and characterize a solid self-microemulsifying drug delivery system (FEL@S-SMEDDS) for felodipine.
• To improve the oral bioavailability and therapeutic efficacy of FEL.
• To evaluate the stability and in vitro release profile of the developed FEL@S-SMEDDS.

Main Methods:

• Optimization of liquid self-microemulsifying drug delivery system (L-SMEDDS) using Response Surface Methodology (RSM).
• Solidification of optimized L-SMEDDS using Neusilin® US2 to form FEL@S-SMEDDS.
• Comprehensive characterization using SEM, DSC, XRD, and stability studies.
• In vitro drug release studies and pharmacokinetic evaluation in rats.

Main Results:

• Optimized FEL@L-SMEDDS exhibited favorable physicochemical properties (e.g., particle size 27.80 nm, PDI 0.074).
• FEL@S-SMEDDS demonstrated excellent stability under accelerated conditions for 6 months.
• Over 90% FEL release within 30 min with a pH-independent profile.
• FEL@S-SMEDDS showed a 2.73-fold increase in Cmax and a 1.46-fold increase in AUC0-24h compared to commercial FEL tablets in rats.

Conclusions:

• FEL@S-SMEDDS is a stable and effective formulation for enhancing FEL oral bioavailability.
• The developed system significantly improves FEL absorption and therapeutic efficacy.
• FEL@S-SMEDDS represents a promising strategy for managing hypertension.