Impact of different hydrophobic ion pairs of octreotide on its oral bioavailability in pigs.
The objective of this study was to investigate the impact of different hydrophobic ion pairs (HIP) on the oral bioavailability of the model drug octreotide in pigs. Octreotide was ion paired with the anionic surfactants deoxycholate, decanoate and docusate differing in lipophilicity. These hydrophobic ion pairs were incorporated in self-emulsifying drug delivery systems (SEDDS) based on BrijO10, octyldodecanol, propylene glycol and ethanol in a concentration of 5mg/ml. SEDDS were characterized regarding size distribution, zeta potential, stability towards lipase, log DSEDDS/release medium and mucus diffusion behavior. The oral bioavailability of octreotide was evaluated in pigs via LC-MS/MS analyses. Most efficient ion pairing was achieved at a molar ratio of 1:3 (peptide: surfactant). SEDDS containing the octreotide-deoxycholate, -decanoate and -docusate ion pair exhibited a mean droplet size of 152nm, 112nm and 191nm and a zeta potential of -3.7, -4.6 and -5.7mV, respectively. They were completely stable towards degradation by lipase and showed a log DSEDDS/release medium of 1.7, 1.8 and 2.7, respectively. The diffusion coefficient of these SEDDS was in the range of 0.03, 0.11 and 0.17×10-9cm2/s, respectively. In vivo studies with these HIPs showed no improvement in the oral bioavailability in case of octreotide-decanoate. In contrast, octreotide-deoxycholate and octreotide-docusate SEDDS resulted in a 17.9-fold and 4.2-fold higher bioavailability vs.


CONTROL
According to these results, hydrophobic ion pairing could be identified as a key parameter for SEDDS to achieve high oral bioavailability.
['Bonengel|Sonja|S|', 'Jelkmann|Max|M|', 'Abdulkarim|Muthanna|M|', 'Gumbleton|Mark|M|', 'Reinstadler|Vera|V|', 'Oberacher|Herbert|H|', 'Prüfert|Felix|F|', 'Bernkop-Schnürch|Andreas|A|']
D000818:Animals D018931:Antineoplastic Agents, Hormonal D001682:Biological Availability D003651:Decanoates D003840:Deoxycholic Acid D004143:Dioctyl Sulfosuccinic Acid D016503:Drug Delivery Systems D065546:Drug Liberation D057927:Hydrophobic and Hydrophilic Interactions D008049:Lipase D008297:Male D015282:Octreotide D013552:Swine
Octreotide Self-emulsifying drug delivery systems Drug release In-vivo study Lipase stability