Novel Microemulsion Systems to Enhance p-Coumaric Acid Oral Bioavailability

Novel p-coumaric acid microemulsion systems were developed to circumvent its absorption and bioavailability challenges. Simplex-lattice mixture design and machine learning methods were employed for optimization. Two optimized formulations were characterized using in vitro re-dispersibility and cytotoxicity on various tumor cell lines (MCF-7, CaCO2, and HepG2). The in vivo bioavailability profiles of the drug loaded in the two microemulsion systems and in the suspension form were compared.

The optimized microemulsions composed of Labrafil M1944 CS (5.67%)/Tween 80 (38.71%)/Labrasol (38.71%)/water (16.92%) and Capryol 90 (0.50%)/Transcutol P (26.67%)/Tween 80 (26.67%)/Labrasol (26.67%)/water (19.50%), respectively. They revealed uniform and stable p-coumaric acid-loaded microemulsion systems with a droplet size diameter of about 10 nm. The loaded microemulsion formulations enhanced the drug re-dispersibility in contrast to the drug suspension which exhibited 5 min lag time.

The loaded formulae were significantly more cytotoxic on all cell lines by 11.98–16.56 folds on MCF-7 and CaCo2 cells and 47.82–98.79 folds on HepG2 cells higher than the pure drug. The optimized microemulsions were 1.5–1.8 times more bioavailable than the drug suspension. The developed p-coumaric acid microemulsion systems could be considered a successful remedy for diverse types of cancer.

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Materials

p-Coumaric acid (HPLC grade > 98%), castor oil, Tween 80 (polysorbate 80), and dialysis membrane with 12,000–14,000 molecular weight cut-offs were purchased from Sigma-Aldrich Chemical Co., Steinheim, Germany. Labrafil M 1944 CS (oleoyl polyoxyl-6 glycerides), Labrasol (caprylocapryol polyoxyl-8 glycerides), Transcutol P (diethylene glycol monoethyl ether), Capryol 90 (propylene glycol caprylate), Maisine CC (glyceryl monolinoleate), Labrafac PG (propylene glycol dicaprylocaprate), Plurol Oleique CC 497 (polyglycerol oleate), Lauroglycol 90 (propylene glycol monolaurate), and Capryol PGMC (propylene glycol monocaprylate) were gently granted by Gattefossé, Saint-Priest, France. Sodium dihydrogen phosphate and disodium hydrogen phosphate were purchased from El Nasr Pharmaceutical Co., Cairo, Egypt. Membrane filter 0.45 µm, 13mm was obtained from Whatman, Kent, UK. PEG 400 (polyethylene glycol 400) was purchased from Nice Chemicals, Kochi, India. Finally, methanol, acetonitrile, and glacial acetic acid were all HPLC grade and were acquired from Fisher Scientific, Loughborough, UK.

Nasser, N., Hathout, R.M., Abd-Allah, H. et al. Simplex Lattice Design and Machine Learning Methods for the Optimization of Novel Microemulsion Systems to Enhance p-Coumaric Acid Oral Bioavailability: In Vitro and In Vivo Studies. AAPS PharmSciTech 25, 56 (2024). https://doi.org/10.1208/s12249-024-02766-1