Digestion of lipid excipients and lipid-based nanocarriers by pancreatic lipase and pancreatin

The digestion behaviour of lipid-based nanocarriers (LNC) has a great impact on their oral drug delivery properties. In this study, various excipients including surfactants, glycerides and waxes, as well as various drug-delivery systems, namely self-emulsifying drug delivery systems (SEDDS), solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were examined via the pH-stat lipolysis model. Lipolysis experiments with lipase and pancreatin revealed the highest release of fatty acids for medium chain glycerides, followed by long chain glycerides and surfactants.

Waxes appeared to be poor substrates with a maximum digestion of up to 10% within 60 min. Within the group of surfactants, the enzymatic cleavage decreased in the following order: glycerol monostearate > polyoxyethylene (20) sorbitan monostearate > PEG-35 castor oil > sorbitan monostearate. After digestion experiments of the excipients, SEDDS, SLN and NLC with sizes between 30 and 300 nm were prepared. The size of almost all formulations was increasing during lipolysis and levelled off after approximately 15 min except for the SLN and NLC consisting of cetyl palmitate. SEDDS exceeded 6000 nm after some minutes and were almost completely hydrolysed by pancreatin. No significant difference was observed between comparable SLN and NLC but surfactant choice and selection of the lipid component had an impact on digestion.

SLN and NLC with cetyl palmitate were only digested by 5% whereas particles with glyceryl distearate were decomposed by 40–80% within 60 min. Additionally, the digestion of the same SLN or NLC, only differing in the surfactant, was higher for SLN/NLC containing polyoxyethylene (20) sorbitan monostearate than PEG-35 castor oil. This observation might be explained by the higher PEG content of PEG-35 castor oil causing a more pronounced steric hindrance for the access of lipase. Generally, digestion experiments performed with pancreatin resulted in a higher digestion compared to lipase. According to these results, the digestion behaviour of LNC depends on both, the type of nanocarrier and on the excipients used for them.

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Materials

Pancreatin from porcine pancreas [4x USP specifications], lipase from porcine pancreas [Type II; 100–500 units/mg protein using olive oil 30 min incubation; 30–90 units/mg protein using triacetin], L-alpha-phosphatidylcholine from egg yolk [60%] (PC), CaCl₂·H₂O, Tris–maleate, Span® 60 (sorbitan monostearate), Kolliphor EL® (PEG-35 castor oil), poloxamer 407 and eugenol were all purchased from Sigma-Aldrich (Vienna, Austria). Sodium taurodeoxycholate hydrate (NaTDC) was bought from Biosynth (Bratislava, Slovakia). Glycerol monostearate, soybean oil and all waxes were obtained from Carl Roth (Karlsruhe, Germany). Tween® 60 (polyoxytheylene (20) sorbitan monostearate, polysorbate 60) was acquired from Gatt Koller (Absam, Austria), Imwitor 742® (medium chain partial glycerides, glyceryl caprylate/caprate Type I) from IOI Oleo GmbH (Hamburg, Germany) and Miglyol® 812 (medium chain triglycerides) from Caesar & Loretz GmbH (Bonn, Germany). Capmul® MCM (mono/di-glyceride of caprylic and capric acid) was kindly provided by Abitec (Columbus, USA), Precirol® ATO 5 (glyceryl distearate) and Maisine^TM 35–1 (glyceryl monolinoleate) by Gattefossé (Saint-Priest, France) as free samples.

Katrin Zöller, Dennis To, Patrick Knoll, Andreas Bernkop-Schnürch,
Digestion of lipid excipients and lipid-based nanocarriers by pancreatic lipase and pancreatin,
European Journal of Pharmaceutics and Biopharmaceutics,
Volume 176, 2022, Pages 32-42, ISSN 0939-6411,
https://doi.org/10.1016/j.ejpb.2022.05.003.