Pharmacokinetics of a natural hybrid-hydrogel formulation of palmitoylethanolamide (PEA): randomized, single-dose, double-blinded, 2-way crossover study

Palmitoylethanolamide (PEA) is an endogenous lipid having the ability to suppress inflammatory responses, restore homeostasis, and modulate pain sensitivity. However, its concentration in the body is often limited, especially on aging, owing to low production and rapid metabolism. PEA supplementation suffers from poor oral bioavailability and half-life. This study was aimed to characterize a natural self-emulsifying hybrid-hydrogel formulation of PEA (P-fen), developed using fenugreek galactomannan seed mucilage (FenuMat®), and further investigate its pharmacokinetics in healthy human volunteers, in comparison with micronized PEA (m-PEA). P-fen was an amorphous powder with a high swelling index and improved solubility (56-fold). It was observed as microspheres of 250 μm size with a porous and smooth surface upon scanning electron microscopy (SEM) analysis. Dynamic light scattering (DLS) analysis indicated ~523 nm particles, with a zeta potential of −60 mV indicating its aqueous stability. In vitro gastrointestinal studies revealed sustained release with better bioaccessibility (>80%). Pharmacokinetics following a single dose of P-fen revealed 5-fold enhancement in bioavailability.