title: Oral self-nanoemulsifying peptide drug delivery systems: impact of lipase on drug release.
abstract: It was the aim of this study to evaluate the impact of lipases on the release behaviour of a peptide drug from oral self-nanoemulsifying drug delivery systems. Octreotide was ion paired with the anionic surfactants deoxycholate, decanoate, oleate and dodecylsulphate. The lipophilic character of these complexes was characterised by determining the n-octanol/buffer pH 7.4 partition coefficient. In the following the most hydrophilic complex was incorporated in a likely lipase degradable self-nanoemulsifying drug delivery systems (SNEDDS) formulation containing a triglyceride (olive oil; Pharm.Eur.) and in a likely not lipase degradable SNEDDS containing lipids and surfactants without any ester bonds. After 1:100 dilutions in artificial intestinal fluid (AIF), the lipid droplets were characterised regarding size distribution. With these SNEDDS, drug release studies were performed in AIF with and without lipase. Results showed that the most hydrophobic complex can be formed with deoxycholate in an octreotide:anionic surfactant ratio of 1:5. Even 73.1 ± 8.1% of it could be quantified in the n-octanol phase. SNEDDS containing octreotide | olive oil | cremophor EL | propylene glycol (2|57|38|3) and octreotide | liquid paraffin | Brij 35 | propylene glycol | ethanol (2|66.5|25|5|1.5) showed after dilution in AIF, a mean droplet size of 232 ± 53 nm and 235 ± 50 nm, respectively. Drug release studies showed a sustained release of octreotide out of these formulations for at least 24 h, whereas > 80% of the drug was released within 2 h in the presence of lipase in the case of the triglyceride containing SNEEDS. In contrast the release profile from ester-free SNEDDS was not significantly altered (p < 0.05) due to the addition of lipase providing evidence for the stability of this formulation towards lipases. According to these results, SNEDDS could be identified as a useful tool for sustained oral peptide delivery taking an enzymatic degradation by intestinal lipases into considerations.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Hamedan University of Medical Sciences , Hamedan , Iran .
authors.forename: Reza
authors.initials: R
authors.lastname: Mahjub
authors.forename: Farid Abedin
authors.initials: FA
authors.lastname: Dorkoosh
authors.forename: Morteza
authors.initials: M
authors.lastname: Rafiee-Tehrani
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop Schnürch
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D065546:Drug Liberation; D004655:Emulsions / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008049:Lipase / Q000378:metabolism*; D015282:Octreotide / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage* / Q000378:metabolism; D014677:Pharmaceutical Vehicles / Q000737:chemistry* / Q000378:metabolism; D013501:Surface-Active Agents / Q000737:chemistry / Q000378:metabolism; D013552:Swine
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004655:Emulsions; D010455:Peptides; D014677:Pharmaceutical Vehicles; D013501:Surface-Active Agents; D008049:Lipase; D015282:Octreotide
keywords: Hydrophobic ion pairing; in vitro release; lipid digestion; octreotide; oral peptide delivery; self-nanoemulsifying drug delivery systems