Omega-3 fatty acid-based self-microemulsifying drug delivery system (SMEDDS) of pioglitazone: Optimization, in vitro and in vivo studies

Pioglitazone (PGL) is an effective insulin sensitizer, however, side effects such as accumulation of subcutaneous fat, edema, and weight gain as well as poor oral bioavailability limit its therapeutic potential for oral delivery. Recent studies have shown that combination of both, PGL and fish oil significantly reduce fasting plasma glucose, improve insulin resistance, and mitigate pioglitazone-induced subcutaneous fat accumulation and weight gain. Nevertheless, developing an effective oral drug delivery system for administration of both medications have not been explored yet. Thus, this study aimed to develop a self-micro emulsifying drug delivery system (SMEDDS) for the simultaneous oral administration of PGL and fish oil. SMEDDS was developed using concentrated fish oil,Tween® 80, and Transcutol HP and optimized by central composite design (CCD). The reconstituted, optimized PGL-SMEDDS exhibited a globule size of 142 nm, a PDI of 0.232, and a zeta potential of −20.9 mV. The in-vitro drug release study of the PGL-SMEDDS showed a first-order model kinetic release and demonstrated remarkable 15-fold enhancement compared to PGL suspension. Additionally, following oral administration in fasting albino Wistar rats, PGL-SMEDDS exhibited 3.4-fold and 1.4-fold enhancements in the AUC_0–24h compared to PGL suspension and PGL marketed product. The accelerated stability testing showed that the optimized SMEDDS formulation was stable over a three-month storage period. Taken together, our findings demonstrate that the developed fish oil-based SMEDDS for PGL could serve as effective nanoplatforms for the oral delivery of PGL, warranting future studies to explore its synergistic therapeutic potential in rats.

2.1. Materials

Sigma-Aldrich, USA was sourced for our supply of PGL (CAS No.: 112529–15-4). Concentrated fish oil (Total Omega-3 Fatty Acids: Minimum 30%) was purchased from Arian Enterprises, Delhi, India. Gift samples of Capryol^TM90 and Transcutol® HP (UNII code: A1A1I8X02B) were generously provided by Gattefosse Pvt. Ltd., Mumbai, India. Capmul®MCM C8 was obtained from Abetic Corporation, Columbus, USA. Both ethyl oleate and Tween® 80 originated from Merck (India). S.D. Fine Chemicals, Ltd. (Mumbai, India) provided us with microcrystalline cellulose, mannitol, soluble starch, and lactose. The Dialysis tubing membrane was purchased from Abron Exports (Haryana, India). All of the solvents used in the experiments were of analytical quality, and HPLC water was utilised throughout.

Download the full article as PDF here: Omega-3 fatty acid-based self-microemulsifying drug delivery system (SMEDDS) of pioglitazone: Optimization, in vitro and in vivo studies

or read it here

Nasr A. Emad, Yasmin Sultana, Mohd Aqil, Asmaa Saleh, Omkulthom Al kamaly, Fahd A Nasr, Omega-3 fatty acid-based self-microemulsifying drug delivery system (SMEDDS) of pioglitazone: Optimization, in vitro and in vivo studies, Saudi Journal of Biological Sciences, Volume 30, Issue 9, 2023, 103778, ISSN 1319-562X,
https://doi.org/10.1016/j.sjbs.2023.103778.