Tablet formulation of Famotidine-loaded P-gp inhibiting nanoparticles using PLA-g-PEG grafted polymer. (7th February 2019)

• Record Type: Journal Article
• Authors: Mokhtar, Mohamed; Gosselin, Patrick M.; François-Xavier, Lacasse; Hildgen, Patrice
• Is Part Of: Pharmaceutical development and technology. Volume 24:Number 2(2019)
• Page Start: 211
• Page End: 221
• Publication Date: 2019-02-07
• Subjects: Caco-2 -- famotidine -- nanoparticles -- permeability -- P-gp -- PLA -- PEG -- tablet; Drug delivery systems -- Periodicals; Pharmaceutical technology -- Periodicals; Drugs -- Administration -- Research -- Periodicals; Drug Delivery Systems -- Periodicals; Pharmaceutical Preparations -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615
• DOI: 10.1080/10837450.2018.1455695
• Languages: English
• ISSNs: 1083-7450

Abstract

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.