In vitro and in vivo evaluation of a pH-, microbiota- and time-based oral delivery platform for colonic release

Colon Drug Delivery Systems Based on Swellable and Microbially Degradable High-Methoxyl Pectin: Coating Process and In Vitro Performance

“…Preliminary trials showed that the viscosity of aqueous solutions having a pectin percentage higher than 2% w/w was excessively high, resulting in sprayability issues. Moreover, to improve the film-forming properties of the polymer and overcome the sticking tendency observed, glycerol at a relatively high concentration and GMS were needed as a plasticizing and an anti-tacking agent, respectively ( Table 4 ) [ 18 , 19 , 20 , 40 ]. Spray-coating was carried out under the operating conditions reported in Table 3 .…”

“…An aqueous solution of HM pectin was prepared by dispersing the polymer powder in deionized water at a concentration of 1.74% w/w under mechanical stirring and heating to 60 °C. A fine dispersion of glycerol monostearate (GMS; 10% on dry polymer mass) was obtained by adding GMS to deionized water and polysorbate (Tween ® 80; 40% on dry GMS mass), heating the mixture to 75 °C for 15 min under magnetic stirring and allowing it to cool to room temperature under vigorous stirring [ 18 , 19 , 20 ]. Glycerol (20% on dry polymer mass) was added to the GMS dispersion before this was mixed with the aqueous HM pectin solution at room temperature under stirring.…”

“…Systems with HM pectin-based coating manufactured by powder-layering were also tested in culture medium (1.5 g/L beef extract, 3 g/L yeast extract, 5 g/L tryptone, 2.5 g/L sodium chloride and 0.3 g/L L-cysteine hydrochloride) adjusted to pH 6.5, sterilized in an autoclave (121 °C for 15 min) and enriched with fecal bacteria to give simulated colonic fluid (SCF) according to current fecal microbiota transplantation (FMT) procedures [ 14 , 18 , 19 , 20 , 47 ]. Frozen aliquots (10 mL) of fecal samples from a young Crohn’s disease patient treated with 5-aminosalicylic acid were allowed to thaw at room temperature before each was added to a flask filled with 90 mL of culture medium and incubated under anaerobic conditions and horizontal shaking (50 rpm) at 37 °C for 24 h [ 20 ].…”

“…The above-described temperature, hydrodynamics and anaerobiosis conditions were maintained throughout the test. At programmed time points, fluid samples (1 mL) were withdrawn, centrifuged at 13,000 rpm for 5 min and filtered (0.22 µm), and the drug released was assayed by HPLC (Nexera-i LC-2040C 3D Plus, Shimadzu, Tokyo, Japan) [ 18 , 19 , 20 ]. A RAPTOR ARC-18 2.7 µm, 150 × 4.6 mm column (Restek Srl, Cernusco sul Naviglio, Italy) was used, and the mobile phase consisted of (A) orthophosphoric acid 0.085% v/v in water and (B) orthophosphoric acid 0.085% v/v in acetonitrile.…”

“…For colon delivery purposes, numerous polysaccharides of natural origin have been exploited [ 10 , 11 ]. These have primarily been incorporated into insoluble or enteric-soluble coatings to trigger release from the core through bacterial degradation once the coated dosage form has entered the large bowel [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Also, they have been used as such to act as matrix-forming or coating agents susceptible to enzymatic breakdown [ 21 , 22 , 23 ].…”