An oral colon delivery platform based on a novel combination strategy, leveraging multiple physiological characteristics of the intestine, is proposed. The system comprises a drug core, a water-swellable/soluble inner layer based on a hydrophilic cellulose derivative and an enteric outer layer (Eudragit® S) containing a microbially-degradable polysaccharide (high-amylose starch, Amylo N460), acting synergistically to prevent early release in the small intestine on the one hand, and release failure on the other. The Eudragit® S:Amylo N460 solid weight ratio in the external coating was 7:3; triethyl citrate and glyceryl monostearate were used as a plasticizer and an anti-tacking agent, respectively. The outer Eudragit® S/Amylo N460 layer was applied in a fluid bed using hydro-alcoholic or aqueous coating formulations. Two types of “inner” systems were studied: (i) Drug-loaded tablets coated with a low-viscosity hydroxypropyl methylcellulose (by aqueous spray-coating), and (ii) hydroxypropyl cellulose capsules prepared by injection-molding (filled with paracetamol as an analytical tracer). The obtained dosage forms were thoroughly characterized, including in vitro release measurements in various media. In all cases, pulsatile release profiles were obtained after medium change from 0.1 N HCl to phosphate buffer pH 7.4, with lag phases depending on the type and preparation technique of the hydrophilic polymer layer. The role of the microbiota on the release performance was explored in simulated colonic fluid (SCF), consisting in culture medium inoculated with fecal samples from inflammatory bowel disease patients. Clear differences in drug release were observed in SCF versus culture medium free of feces, indicating the effect of microbial degradation.

Oral colon delivery platform based on a novel combination approach: Design concept and preliminary evaluation / S. Moutaharrik, A. Maroni, A. Melocchi, L. Zema, A.A. Foppoli, M. Cerea, L. Palugan, C. Neut, F. Siepmann, J. Siepmann, A. Gazzaniga. - In: JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY. - ISSN 1773-2247. - 66(2021 Dec), pp. 102919.1-102919.9. [10.1016/j.jddst.2021.102919]

Oral colon delivery platform based on a novel combination approach: Design concept and preliminary evaluation

S. Moutaharrik
Primo
;
A. Maroni
Secondo
;
A. Melocchi;L. Zema;A.A. Foppoli;M. Cerea;L. Palugan;A. Gazzaniga
Ultimo
2021

Abstract

An oral colon delivery platform based on a novel combination strategy, leveraging multiple physiological characteristics of the intestine, is proposed. The system comprises a drug core, a water-swellable/soluble inner layer based on a hydrophilic cellulose derivative and an enteric outer layer (Eudragit® S) containing a microbially-degradable polysaccharide (high-amylose starch, Amylo N460), acting synergistically to prevent early release in the small intestine on the one hand, and release failure on the other. The Eudragit® S:Amylo N460 solid weight ratio in the external coating was 7:3; triethyl citrate and glyceryl monostearate were used as a plasticizer and an anti-tacking agent, respectively. The outer Eudragit® S/Amylo N460 layer was applied in a fluid bed using hydro-alcoholic or aqueous coating formulations. Two types of “inner” systems were studied: (i) Drug-loaded tablets coated with a low-viscosity hydroxypropyl methylcellulose (by aqueous spray-coating), and (ii) hydroxypropyl cellulose capsules prepared by injection-molding (filled with paracetamol as an analytical tracer). The obtained dosage forms were thoroughly characterized, including in vitro release measurements in various media. In all cases, pulsatile release profiles were obtained after medium change from 0.1 N HCl to phosphate buffer pH 7.4, with lag phases depending on the type and preparation technique of the hydrophilic polymer layer. The role of the microbiota on the release performance was explored in simulated colonic fluid (SCF), consisting in culture medium inoculated with fecal samples from inflammatory bowel disease patients. Clear differences in drug release were observed in SCF versus culture medium free of feces, indicating the effect of microbial degradation.
Oral colon delivery; combined time-; pH- and microbiota-dependent approach; hydroxylpropyl methylcellulose; hydroxypropyl cellulose; Eudragit® S; high-amylose starch; spray-coating
Settore CHIM/09 - Farmaceutico Tecnologico Applicativo
20-ott-2021
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/883408
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