Tablet formulation of Famotidine-loaded P-gp inhibiting nanoparticles using PLA-g-PEG grafted polymer |
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Authors: | Mohamed Mokhtar Patrick M Gosselin Lacasse François-Xavier Patrice Hildgen |
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Affiliation: | 1. Faculté de Pharmacie, Université de Montréal, Montreal, Canada;2. Faculty of Health Science, Sirte University, Sirte, Libya;3. Pharmaceutical R&4. D, Corealis Pharma Inc, Laval, Canada |
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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. |
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Keywords: | Caco-2 famotidine nanoparticles permeability P-gp PLA PEG tablet |
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