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.

Guar gum as a microbially degradable component for an oral colon delivery system based on a combination strategy: formulation and in vitro evaluation / S. Moutaharrik, G. Meroni, A. Soggiu, A.A. Foppoli, M. Cerea, L. Palugan, F. Caloni, P.A.M. Martino, A. Gazzaniga, A. Maroni. - In: DRUG DELIVERY AND TRANSLATIONAL RESEARCH. - ISSN 2190-3948. - 14:(2023), pp. 826-838. [10.1007/s13346-023-01439-z]

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

S. Moutaharrik
Primo
;
G. Meroni
Secondo
;
A. Soggiu;A.A. Foppoli;M. Cerea;L. Palugan;F. Caloni;P.A.M. Martino
;
A. Gazzaniga
Penultimo
;
A. Maroni
Ultimo
2023

Abstract

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.
Film-coating; In vitro release test; Intestinal microbiota; Intestinal pH; Intestinal transit time; Oral colon drug delivery;
Settore CHIM/09 - Farmaceutico Tecnologico Applicativo
Settore VET/05 - Malattie Infettive degli Animali Domestici
Settore VET/07 - Farmacologia e Tossicologia Veterinaria
2023
12-ott-2023
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1015649
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