Guar gum as a microbially degradable component for an oral colon delivery system based on a combination strategy: formulation and in vitro evaluation

Oral colon delivery has widely been pursued exploiting naturally occurring polysaccharides degraded by the resident microbiota. However, their hydrophilicity may hinder the targeting performance. The aim of the present study was to manufacture and evaluate a double-coated delivery system leveraging intestinal microbiota, pH, and transit time for reliable colonic release. This system comprised a tablet core, a hydroxypropyl methylcellulose (HPMC) inner layer and an outer coating based on Eudragit^® S and guar gum. The tablets were loaded with paracetamol, selected as a tracer drug because of the well-known analytical profile and lack of major effects on bacterial viability. The HPMC and Eudragit^® S layers were applied by film-coating. Tested for in vitro release, the double-coated systems showed gastroresistance in 0.1 N HCl followed by lag phases of consistent duration in phosphate buffer pH 7.4, imparted by the HPMC layer and synergistically extended by the Eudragit^® S/guar gum one. In simulated colonic fluid with fecal bacteria from an inflammatory bowel disease patient, release was faster than in the presence of β-mannanase and in control culture medium. The bacteria-containing fluid was obtained by an experimental procedure making multiple tests possible from a single sampling and processing run. Thus, the study conducted proved the feasibility of the delivery system and ability of guar gum to trigger release in the presence of colon bacteria without impairing the barrier properties of the coating. Finally, it allowed an advantageous simulated colonic fluid preparation procedure to be set up, reducing the time, costs, and complexity of testing and enhancing replicability.

Materials

Paracetamol for direct compression (Rhodapap™ DC 90, Novacyl, Lyon, France); microcrystalline cellulose (Avicel® PH-101, FMC Co, San Colombano al Lambro, Italy); sodium starch glycolate (Explotab® CLV, JRS Rettenmaier Italia, Castenedolo, Italy); vinylpyrrolidone-vinyl acetate copolymer (Kollidon® VA 64, BASF Italia Spa, Cesano Maderno, Italy); hydrophilic fumed silica (Aerosil® 200, Evonik Degussa Italia Spa, Pandino, Italy); magnesium stearate (Carlo Erba Reagents Srl, Cornaredo, Italy); hydroxypropyl methylcellulose, HPMC (Methocel™ E50, Colorcon Ltd, Dartford, United Kingdom); polyethylene glycol, PEG 400 (Clariant SE, Sulzbach am Taunus, Germany); methacrylic acid-methyl methacrylate copolymer (1:2), EuS (Eudragit® S, Evonik Degussa Italia Spa); guar gum, GG (Gasid, Volvera, Italy), viscosity of 1% aqueous solution at 25 °C 3620 cps, d10 = 24.6, d50 = 56.1, d90 = 125.0; triethyl citrate, TEC (Honeywell International Inc, Charlotte, North Carolina, United States); glyceryl monostearate, GMS (Gattefossé SA, Saint-Priest, France); polysorbate 80, Tween® 80 (ACEF Spa, Fiorenzuola d’Arda, Italy); ammonia solution 25% v/v (Carlo Erba Reagents Srl); ethanol 96% v/v (VWR International Srl, Milan, Italy); bovine serum albumin, BSA (Merck KgaA, Darmstadt, Germany); endo-1,4-β-mannanase from Cellvibrio japonicus 5000 U/mL (E-BMACJ, Megazyme Ltd, Bray, Ireland); beef extract (ThermoFisher Scientific, Rodano, Italy); yeast extract (ThermoFisher Scientific); tryptone (ThermoFisher Scientific); sodium chloride (Carlo Erba Reagents Srl); L-cysteine hydrochloride (ThermoFisher Scientific); glycerol 99% (Carlo Erba Reagents Srl); sterile gauze swabs (Rays Spa, Osimo, Italy).

Read more

Moutaharrik, S., Meroni, G., Soggiu, A. et al. Guar gum as a microbially degradable component for an oral colon delivery system based on a combination strategy: formulation and in vitro evaluation. Drug Deliv. and Transl. Res. (2023).
https://doi.org/10.1007/s13346-023-01439-z

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