G-3371

Development of a novel self-microemulsifying drug delivery system for enhancing the intestinal absorption of aprepitant: formulation, in vitro characterization, and in situ permeation assessment.

 Atabak Sharafatmand ¹ ℗, Seyedeh Giso Akbarian ², Dr. Ziba Islambulchilar ³ ©, Dr. Parvin Zakeri-Milani ⁴, Dr. Hadi Valizadeh ⁵   

 
Abstract

Introduction: Aprepitant, an antagonist of the NK1 receptor, is widely used to prevent and treat nausea and vomiting induced by chemotherapy. It is a BCS Class II compound with poor aqueous solubility and low oral bioavailability, which contributes to reduced therapeutic effects and unpredictable clinical efficacy. These limitations are mainly due to poor dissolution and extensive first-pass metabolism. This study aims to develop a self-nanoemulsifying drug delivery system (SNEDDS) for aprepitant to improve its solubility and intestinal permeability. Material method: In this research, an SNEDDS was developed through an experimental design from oleic acid as oil phase, Tween 80 as surfactant, and transkitol P as solvent. D-optimal design has been used to design and optimize the ratio of formulation components. The study employed the single-pass intestinal perfusion (SPIP) method in an attempt to assess intestinal permeability. This technique involved cannulation of rat jejunum, controlled rate of drug perfusion, and determination of effective intestinal permeability (Peff) by the ratio of corrected concentration at outlet to inlet concentration of the drug. Results: The optimal formulation of components was determined as oleic acid 10%, Tween 80 60%, and 30% Transcutol P. The particle size of the aprepitant-loaded SMEDDS was measured at 152 nm, with a polydispersity index (PDI) of 0.35. The optimized aprepitant-loaded SMEDDS exhibited a zeta potential of -21 ± 8 mV. The intestinal permeability of aprepitant at a concentration of 20 μg/mL was calculated to (78.5 ± 18.5) × 10 -4 cm/s. The numerical value (Peff) of the self-nanoemulsifying drug delivery system containing aprepitant was calculated to be (173.5 ± 37.7) × 10 -4cm/s. Discussion and Conclusion: The limited bioavailability of aprepitant necessitates measures for increasing its absorption. Experimental studies prove that the use of SNEDDS enhances the permeability of aprepitant through the intestine considerably. This enhancement may be attributed to various mechanisms, involving the use of excipients like Tween, thereby leading to absorption along lymphatic routes, enterocytes, endocytosis, and selective paracellular transport. Lastly, entrapment of aprepitant within an SNEDDS not only increases its oral permeability but also results in increased drug bioavailability.

Keywords: SPIP, aprepitant, intestinal permeability, SNEDDS