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.

Preparation, Box-Behnken Statistical Optimization, and In Vitro Characterization of a Self-nanoemulsifying Drug Delivery System for the Oral Delivery of Budesonide as a Poorly Soluble Drug

“…Therefore, the observed slowrelease rate of budesonide from SNEDDS preparation is favourable. The obtained in vitro release profile is in accordance with the findings of Mahjub et al (33). Based on their results, SNEDDS prepared from liquid paraffin as the oil phase exhibited more stability against lipase activity in the GI and was considered as the lipase-undegradable SNEDDS that poses a slower release rate of octreotide compared to SNEDDS prepared from the olive oil as the oil phase.…”

Hydrophobic ion pairing: encapsulating small molecules, peptides, and proteins into nanocarriers

“…Screening multiple drug : counterion molar ratios is a straightforward series of experiments to perform. By doing so, researchers have measured how a number of important parameters vary with charge ratio: complexation efficiency, 18,51,57,[86][87][88][90][91][92][93][94][95][96][97][98] complex log P 50,98-100 and zeta potential, 93,101,102 drug encapsulation efficiency, 30 and even droplet size in a SEDDS (self-emulsifying drug delivery system). 94 Complexation efficiency in water is typically measured by centrifuging precipitated complexes and measuring the amount of free drug in the supernatant.…”

Injectables and Depots to Prolong Drug Action of Proteins and Peptides

“…An oral formulation of cyclosporine developed by Novartis and based on SEDDSs is currently on the market (Sandimmun Neoral ® ), while an insulin SEDDS formulation is in Phase III clinical trials [ 269 , 270 ]. SEDDSs for the delivery of a number of other peptides, including octreotide [ 258 ] and leuprolide [ 259 ], have also been described by different research groups ( Table 3 ). SEDDSs offer the advantages of being simple to produce with batch uniformity and being cost-effective, making them very promising for oral protein and peptide delivery [ 269 ].…”