TY - JOUR
T1 - Adjustment of triple shellac coating for precise release of bioactive substances with different physico-chemical properties in the ileocolonic region
AU - Theismann, Eva Maria
AU - Keppler, Julia Katharina
AU - Knipp, Jörg Rainer
AU - Fangmann, Daniela
AU - Appel, Esther
AU - Gorb, Stanislav N.
AU - Waetzig, Georg H.
AU - Schreiber, Stefan
AU - Laudes, Matthias
AU - Schwarz, Karin
PY - 2019/6/10
Y1 - 2019/6/10
N2 - Formulations for the controlled release of substances in the human terminal ileum and colon are essential to target the gut microbiome and its interactions with the intestinal mucosa. In contrast to pharmaceutical enteric coatings, reliable food-grade alternatives are still scarce. Shellac coatings have been used for various active ingredients, but their stability is affected by the physicochemical properties of the encapsulated substances. It is well known, that shellac release can be modulated by an acidic subcoating. Here, we hypothesized that a triple shellac coating with an adjusted intermediate coating (acidic or alkaline) can be effectively used to counteract the differences in pH value of various encapsulated substances, allowing a precise targeting of the desired release pH value. First, the system was tested with riboflavin 5′-monophosphate sodium salt dihydrate (RMSD) as a characteristic model substance. Secondly, it was transferred to nicotinic acid (NA) and nicotinamide (NAM) as bioactive compounds with different physio-chemical properties: NAM, an alkaline crystalline and highly water-soluble substance, led to a premature release from conventional shellac microcapsules, whereas RMSD and NA with their medium solubility and neutral to acidic pH properties delayed the shellac dissolution. A precise modulation of the release profile of each substance was possible by the addition of different intermediate subcoatings: an acidic layer with citric acid counteracted the premature release of the alkaline and highly soluble NAM. In contrast, an alkaline sodium bicarbonate intermediate subcoating enhanced shellac swelling and delayed the release of NA and RMSD. In conclusion, the novel triple-layer shellac coating provides a much higher adaptability and reliability for nutritional formulations aiming at a targeted release in the ileocolonic region.
AB - Formulations for the controlled release of substances in the human terminal ileum and colon are essential to target the gut microbiome and its interactions with the intestinal mucosa. In contrast to pharmaceutical enteric coatings, reliable food-grade alternatives are still scarce. Shellac coatings have been used for various active ingredients, but their stability is affected by the physicochemical properties of the encapsulated substances. It is well known, that shellac release can be modulated by an acidic subcoating. Here, we hypothesized that a triple shellac coating with an adjusted intermediate coating (acidic or alkaline) can be effectively used to counteract the differences in pH value of various encapsulated substances, allowing a precise targeting of the desired release pH value. First, the system was tested with riboflavin 5′-monophosphate sodium salt dihydrate (RMSD) as a characteristic model substance. Secondly, it was transferred to nicotinic acid (NA) and nicotinamide (NAM) as bioactive compounds with different physio-chemical properties: NAM, an alkaline crystalline and highly water-soluble substance, led to a premature release from conventional shellac microcapsules, whereas RMSD and NA with their medium solubility and neutral to acidic pH properties delayed the shellac dissolution. A precise modulation of the release profile of each substance was possible by the addition of different intermediate subcoatings: an acidic layer with citric acid counteracted the premature release of the alkaline and highly soluble NAM. In contrast, an alkaline sodium bicarbonate intermediate subcoating enhanced shellac swelling and delayed the release of NA and RMSD. In conclusion, the novel triple-layer shellac coating provides a much higher adaptability and reliability for nutritional formulations aiming at a targeted release in the ileocolonic region.
KW - Colon
KW - Enteric coating
KW - Fluidized-bed
KW - Shellac
KW - Subcoat
KW - Targeted release
U2 - 10.1016/j.ijpharm.2019.04.039
DO - 10.1016/j.ijpharm.2019.04.039
M3 - Article
C2 - 30991131
AN - SCOPUS:85064946253
SN - 0378-5173
VL - 564
SP - 472
EP - 484
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
ER -