Recent progress in pharmaceutical excipients as P-glycoprotein inhibitors for potential improvement of oral drug bioavailability: A comprehensive overview

Abstract

Pharmaceutical excipients such as P-glycoprotein inhibitors can also increase the solubility and affinity of drugs to the intestinal membrane, enhance paracellular pathways and endocyte uptake, and activate lymph transport pathways, thereby increasing the bioavailability of oral drugs. This review aims to review and assess the performance of pharmaceutical excipients as P-glycoprotein permeability inhibitors in improving oral drug bioavailability in drug formulations by evaluating meta data from P-glycoprotein efflux in permeability and pharmacokinetics studies.

The review results are pharmaceutical excipients that have proven effective as P-glycoprotein inhibitors from the surfactant and polymer groups, namely TPGS and Poloxamer 188, respectively. All nanosystems incorporating pharmaceutical excipients as P-gp inhibitors show potential in enhancing the permeability and bioavailability of oral drugs when compared to conventional formulations. The effectiveness of these systems has been evaluated through in vitro (Caco-2 cells), ex vivo (everted gut sac), in situ (SPIP), and in vivo (AUC) methods.

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Table 2. The excipients as P-gp inhibitors

Type	Group	Material	References
Surfactant	Polysorbates	– Polysorbate 80	(Constantinides and Wasan 2007; Kou et al. 2018)
	Polysorbates	– Polysorbate 20
	Sucrose esters	Sucrose monolaurate
	Tocopheryl ester	Tocopheryl polyethylene glycol succinate (TPGS)
	PEG esters	– PEG-35 castor oil (Cremophor^® EL)
		– PEG-12-hydroxystearate (Kolliphor^® HS 15/Solutol^® HS-15)
		– PEG-8 glyceryl caprylate/caprate (Labrasol^®)
		– PEG-6 glyceryl caprylate/caprate (Softigen^® 767)
		– PEG-32 Glyceryl laureate (Gelucire 44/14)
		– Polyoxyethylene (40) stearate (Myrj 52)
	PEG ethers	Polyoxyethylene (20) stearyl ether (Brij 78)
	Others	– Natrium 1,4-bis (2-etilheksioksi)-1,4 – dioxobutane– 2-sulfonate (AOT)
	Others	– Cetyltrimethylammonium bromide (CTAB)
Polymer	Natural polymers	Dextrans, Agar, Gellan gum, Gum arabic, Gum traganth, Guar gum, Carrageenan gum, Xanthan gum, Alginates, Chitosan.	(Constantinides and Wasan 2007; Kou et al. 2018)
	Amphiphilic diblock copolymers	– MethoxyPEG-block-polycaprolactone (MePEG-b-PCL)
	Amphiphilic diblock copolymers	– Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer (Soluplus^®)
	Pluronic block copolymers	– Pluronic F127/Poloxamer 407
	Pluronic block copolymers	– Pluronic F68/Poloxamer 188
Lipid-based excipients	Glycerides	– Monoolein (Peceol^TM)	(Constantinides and Wasan 2007; Kou et al. 2018)
	Glycerides	– Monostearin
	Phospholipids	– 1,2-dioctanoyl-sn-glycero-3-phosphocholine (8:0 PC)
	Phospholipids	– 1,2-didecanoyl-sn-glycero-3-phosphocholine (10:0 PC)
	Methylated cyclodextrin	Methyl-β-cyclodextrin

Darusman F, Rusdiana T, Sopyan I, Rahma H, Hanifa M (2025) Recent progress in pharmaceutical excipients as P-glycoprotein inhibitors for potential improvement of oral drug bioavailability: A comprehensive overview. Pharmacia 72: 1–16. https://doi. org/10.3897/pharmacia.72.e140734