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<p>Felodipine (FEL), a first-line antihypertensive drug, suffers from low oral bioavailability due to its poor aqueous solubility and first-pass metabolism. This study aimed to enhance the oral bioavailability of FEL by developing a solid self-microemulsifying drug delivery system (FEL@S-SMEDDS). Initially, a pseudo-ternary phase diagram was constructed via the water titration method to identify the optimal oil phase, surfactant, and co-surfactant. The liquid SMEDDS (FEL@L-SMEDDS) was optimized using Response Surface Methodology (RSM), resulting in a composition of 8.91% FEL (drug loading), 22.77% ethyl oleate, 47.30% EL 35, and 21.02% Transcutol HP. The FEL@L-SMEDDS exhibited a spherical-like morphology with an average particle size of 27.80&#xa0;nm, a PDI of 0.074, a zeta potential of -3.44&#xa0;mV, an emulsification time of 34&#xa0;s, and a transmittance of 96.1%. Following the establishment of this optimized liquid system, FEL@L-SMEDDS was solidified using Neusilin® US2 at a liquid-to-solid mass ratio of 1.5:1 to obtain FEL@S-SMEDDS, which was comprehensively characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). In terms of stability, FEL@S-SMEDDS exhibited excellent performance under accelerated conditions (40 ± 2℃, 75 ± 5% relative humidity) for 6&#xa0;months. Regarding <i>in vitro</i> release behavior, FEL@S-SMEDDS afforded over 90% drug release within 30&#xa0;min across different dissolution media, exhibiting a pH-independent release profile. Ultimately, the efficacy of this formulation was validated through pharmacokinetic evaluations in rats, revealing that the peak drug concentration (C<sub>max</sub>) and area under the drug concentration–time curve (AUC<sub>0-24&#xa0;h</sub>) of FEL@S-SMEDDS were increased by 2.73-fold and 1.46-fold higher than those of commercial FEL tablet, respectively. In conclusion, FEL@S-SMEDDS represents a promising strategy for enhancing the oral bioavailability and therapeutic efficacy of FEL in hypertension management.</p> Graphic Abstract <p></p>

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

  • 期刊论文

  • 发表日期：

    2026年2月19日

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  • Ying Zheng,
  • Lusi Chen,
  • Yingshu Feng,
  • Caleb Kesse Firempong,
  • Dongli Li,
  • Guoqing Zhang,
  • Hongfei Liu

摘要

Felodipine (FEL), a first-line antihypertensive drug, suffers from low oral bioavailability due to its poor aqueous solubility and first-pass metabolism. This study aimed to enhance the oral bioavailability of FEL by developing a solid self-microemulsifying drug delivery system (FEL@S-SMEDDS). Initially, a pseudo-ternary phase diagram was constructed via the water titration method to identify the optimal oil phase, surfactant, and co-surfactant. The liquid SMEDDS (FEL@L-SMEDDS) was optimized using Response Surface Methodology (RSM), resulting in a composition of 8.91% FEL (drug loading), 22.77% ethyl oleate, 47.30% EL 35, and 21.02% Transcutol HP. The FEL@L-SMEDDS exhibited a spherical-like morphology with an average particle size of 27.80 nm, a PDI of 0.074, a zeta potential of -3.44 mV, an emulsification time of 34 s, and a transmittance of 96.1%. Following the establishment of this optimized liquid system, FEL@L-SMEDDS was solidified using Neusilin® US2 at a liquid-to-solid mass ratio of 1.5:1 to obtain FEL@S-SMEDDS, which was comprehensively characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). In terms of stability, FEL@S-SMEDDS exhibited excellent performance under accelerated conditions (40 ± 2℃, 75 ± 5% relative humidity) for 6 months. Regarding in vitro release behavior, FEL@S-SMEDDS afforded over 90% drug release within 30 min across different dissolution media, exhibiting a pH-independent release profile. Ultimately, the efficacy of this formulation was validated through pharmacokinetic evaluations in rats, revealing that the peak drug concentration (Cmax) and area under the drug concentration–time curve (AUC0-24 h) of FEL@S-SMEDDS were increased by 2.73-fold and 1.46-fold higher than those of commercial FEL tablet, respectively. In conclusion, FEL@S-SMEDDS represents a promising strategy for enhancing the oral bioavailability and therapeutic efficacy of FEL in hypertension management.

Graphic Abstract