title: Hydrophobic ion pairing: Key to highly payloaded self-emulsifying peptide drug delivery systems.
abstract: OBJECTIVE
  The aim of this study was the formation and characterization of various ion pairs of therapeutic peptides with different surfactants in order to reach a high payload in self-emulsifying drug delivering systems (SEDDS).
  
  
  METHODS
  Hydrophobic ion pairs (HIP) were formed between the anionic surfactants sodium docusate, dodecylsulfate and oleate and the peptides leuprorelin (LEU), insulin (INS) and desmopressin (DES). The efficiency of HIP formation was evaluated by quantifying the amount of formed complexes, log P value determination in n-octanol/water via HPLC and zeta potential measurements. Solvents and surfactants were screened regarding their complex solubilizing properties. Subsequently, peptide complexes were incorporated into SEDDS followed by payload and stability determination.
  
  
  RESULTS
  Independent from the type of peptide, docusate showed the most efficient HIP properties followed by dodecylsulfate and oleate. Ratios of 2:1 for LEU, 6:1 for INS and 1.5:1 for DES led to the highest quantity of formed complexes with docusate and log P increased at least by 3 units. The more docusate was added to each peptide, the more negative became the zeta potential of the resulting complex. Incorporating these optimized complexes into novel SEDDS containing Capryol 90, Labrafil M 2125 CS, Labrasol ALF, Peceol, propylene glycol, tetraglycol, Transcutol HP and Tween 20 allowed payloads of the LEU, DES and INS complexes above 10%. Moreover, SEDDS exhibited high stability and constant negative zeta potential over a 4h incubation time.
  
  
  CONCLUSIONS
  Following the procedure described herein payloads >10% can be achieved for peptide drugs in SEDDS.
authors.affiliation: Thiomatrix Forschungs-und Beratungs GmbH, Trientlgasse 65, Innsbruck, Austria.
authors.forename: Janine
authors.initials: J
authors.lastname: Griesser
authors.affiliation: Thiomatrix Forschungs-und Beratungs GmbH, Trientlgasse 65, Innsbruck, Austria.
authors.forename: Gergely
authors.initials: G
authors.lastname: Hetényi
authors.affiliation: Thiomatrix Forschungs-und Beratungs GmbH, Trientlgasse 65, Innsbruck, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Moser
authors.affiliation: Gattefossé SAS, 36 chemin de Genas, 69804 Saint-Priest Cedex, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Demarne
authors.affiliation: Gattefossé SAS, 36 chemin de Genas, 69804 Saint-Priest Cedex, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Jannin
authors.affiliation: Thiomatrix Forschungs-und Beratungs GmbH, Trientlgasse 65, Innsbruck, Austria; Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. Electronic address: andreas.bernkop@uibk.ac.at.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000737:chemistry; D004143:Dioctyl Sulfosuccinic Acid / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D045703:Emulsifying Agents / Q000008:administration & dosage / Q000737:chemistry*; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D007328:Insulin / Q000008:administration & dosage / Q000737:chemistry; D016729:Leuprolide / Q000008:administration & dosage / Q000737:chemistry; D019301:Oleic Acid / Q000008:administration & dosage / Q000737:chemistry; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry*; D012967:Sodium Dodecyl Sulfate / Q000008:administration & dosage / Q000737:chemistry; D012995:Solubility
chemical_list: D045703:Emulsifying Agents; D004655:Emulsions; D007328:Insulin; D010455:Peptides; D004143:Dioctyl Sulfosuccinic Acid; D019301:Oleic Acid; D012967:Sodium Dodecyl Sulfate; C013173:osteum; D016729:Leuprolide; D003894:Deamino Arginine Vasopressin
keywords: Desmopressin; Hydrophobic ion paring; Insulin; Leuprorelin; Peptide delivery; Self-emulsifying drug delivery systems