Tablet formulation of Famotidine-loaded P-gp inhibiting nanoparticles using PLA-g-PEG grafted polymer

Abstract

Our work aimed at evaluating the use of permeability glycoprotein (P-gp) inhibiting nanoparticles (NPs) as a part of a suitable oral solid dosage to improve bioavailability. Famotidine (Pepcid^®), a stomach acid production inhibitor, was used as a drug model to test our hypothesis. Famotidine-loaded NPs were prepared by solvent emulsion evaporation using PEG grafted on a polylactide acid (PLA) polymer backbone (PLA-g-PEG), with a 5% molar ratio of PEG versus lactic acid monomer and PEG of either 750 or 2000 Da molecular weight. Tablet formulation was composed of 40% Famotidine-loaded NPs, 52.5% microcrystalline cellulose as filler, 7% pre-gelatinized starch as binder/disintegrant, and 0.5% magnesium stearate as lubricant. Tablets containing 1.6 mg of Famotidine were prepared at an average weight of 500 mg, thickness of 6.2–6.5 mm, hardness of 5–8 kp, and disintegration time of <1 min. Our results suggest that Famotidine-loaded NPs using grafted PEG-g-PLA polymers can be formulated as an oral solid dosage form while effectively inhibiting P-gp mediated Famotidine efflux, irrespective of PEG molecular weights. This could therefore represent an attractive formulation alternative to enhance oral permeability and bioavailability of drugs that are P-gp substrates.

Keywords:

• Caco-2
• famotidine
• nanoparticles
• permeability
• P-gp
• PLA
• PEG
• tablet

Acknowledgements

The authors wish to thank COREALIS Pharma Inc, Montreal for their help in doing some analysis.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Additional information

Funding

This work was supported in part by a grant of Fond Quebecois de la Recherche en Nature et Technologie (FQRNT). Mohamed Mokhtar thanks the Ministry of Higher Education, Libya for granting him a scholarship during his Ph.D.