Presentation Information
[P04-591]Fenofibrate-Loaded SMEDDS to Reduce Food Effect and Enhance Oral Bioavailability
○Saeeun Ryu1, Pil-Jae Song1, Min-Jae Kim1, Dae-Duk Kim1 (1. Seoul National University (Korea))
Keywords:
Self-microemulsifying drug delivery system,Lipid-based formulation,Fenofibrate,Poorly water-soluble drugs,BCS Class II,Food effect,Oral bioavailability,Pharmacokinetics
The variable absorption of lipophilic drugs influenced by food intake poses a significant challenge to clinical efficacy and patient adherence. Although various formulation strategies have been explored to mitigate this food effect, limitations such as thermodynamic instability and the requirement of high therapeutic doses remain prevalent. This study aimed to develop an optimized self-microemulsifying drug delivery system (SMEDDS) for fenofibrate, a BCS Class II drug characterized by high lipophilicity (Log P = 5.2) and low aqueous solubility, to overcome its dissolution-rate limited absorption, thereby improving oral bioavailability and minimizing pharmacokinetic variability between fed and fasted states.
The optimal composition of oil, surfactant, and co-surfactant was determined through solubility screening and pseudo-ternary phase diagram analysis to ensure maximum drug loading and formulation stability. Physicochemical characterization using transmission electron microscopy (TEM) and dynamic light scattering (DLS) confirmed that the optimized SMEDDS spontaneously formed homogeneous spherical microemulsions with a mean droplet size of approximately 50 nm upon aqueous dispersion.
In vivo pharmacokinetic studies in rats demonstrated that the SMEDDS formulation significantly enhanced oral bioavailability compared with the commercial reference formulation. Specifically, the systemic exposure (AUC) of SMEDDS increased by 2.07-fold and 4.14-fold relative to the reference under fed and fasted conditions, respectively. Moreover, the food effect index (FEI) improved from 1.70 (reference) to 0.85 (SMEDDS), indicating a reduced food effect for fenofibrate.
In conclusion, the developed SMEDDS effectively overcomes dissolution-rate limited absorption and minimizes the food-dependent variability in fenofibrate pharmacokinetics. These findings suggest that the optimized SMEDDS represents a promising strategy for enhancing the oral bioavailability of poorly water-soluble drugs and potentially alleviating the clinical constraint associated with administration with meals.
The optimal composition of oil, surfactant, and co-surfactant was determined through solubility screening and pseudo-ternary phase diagram analysis to ensure maximum drug loading and formulation stability. Physicochemical characterization using transmission electron microscopy (TEM) and dynamic light scattering (DLS) confirmed that the optimized SMEDDS spontaneously formed homogeneous spherical microemulsions with a mean droplet size of approximately 50 nm upon aqueous dispersion.
In vivo pharmacokinetic studies in rats demonstrated that the SMEDDS formulation significantly enhanced oral bioavailability compared with the commercial reference formulation. Specifically, the systemic exposure (AUC) of SMEDDS increased by 2.07-fold and 4.14-fold relative to the reference under fed and fasted conditions, respectively. Moreover, the food effect index (FEI) improved from 1.70 (reference) to 0.85 (SMEDDS), indicating a reduced food effect for fenofibrate.
In conclusion, the developed SMEDDS effectively overcomes dissolution-rate limited absorption and minimizes the food-dependent variability in fenofibrate pharmacokinetics. These findings suggest that the optimized SMEDDS represents a promising strategy for enhancing the oral bioavailability of poorly water-soluble drugs and potentially alleviating the clinical constraint associated with administration with meals.
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