title: Development and in vitro evaluation of an oral SEDDS for desmopressin.
abstract: BACKGROUND
  Self-emulsifying drug delivery systems (SEDDS) are among most promising tools for improving oral peptide bioavailability.
  
  
  OBJECTIVE
  In this study, in vitro protective effect of SEDDS containing desmopressin against presystemic inactivation by glutathione and α-chymotrypsin was evaluated.
  
  
  METHODS
  The partitioning coefficient (log P) of desmopressin was increased via hydrophobic ion pairing using anionic surfactants. Solubility studies were performed to select the appropriate solvents for SEDDS preparation. Subsequently, droplet size and emulsification properties of 22 SEDDS formulations were evaluated. Moreover, the peptide-surfactant complex was dissolved in two chosen SEDDS formulations. Finally, SEDDS containing desmopressin were characterized regarding lipase stability, toxicity, and in vitro protective effect toward glutathione and α-chymotrypsin.
  
  
  RESULTS
  Desmopressin log P was increased from initial -6.13 to 0.33 using sodium docusate. The resulting desmopressin docusate complex (DES/AOT) was incorporated in two different SEDDS formulations, containing Capmul 907 P as main solvent. DES/AOT-SEDDS-F4 (containing 0.07% w/w DES/AOT) was composed of 50% Capmul 907P, 40% Cremophor RH40, and 10% Transcutol. The comparatively more hydrophilic formulation DES/AOT-SEDDS-F15 (containing 0.25% w/w DES/AOT) consisted of 20% Capmul 907P, 40% Acconon MC8-2, and 40% Tween 20. Both formulations were stable toward digestion by lipase and protected desmopressin toward α-chymotrypsin degradation. Moreover, DES/AOT-SEDDS-F4 also protected the peptide from thiol/disulfide exchange reactions with glutathione and was not cytotoxic at a concentration of 0.375% (w/w).
  
  
  CONCLUSIONS
  DES/AOT-SEDDS-F4 protected desmopressin from in vitro glutathione and α-chymotrypsin degradation. DES/AOT-SEDDS-F4 was metabolically stable and nontoxic. Therefore, it could be considered as a potential delivery system for oral desmopressin administration.
authors.affiliation: a Department of Pharmaceutical Technology , Institute of Pharmacy, Leopold-Franzens-University Innsbruck , Innsbruck , Austria/Europe and.
authors.forename: Ožbej
authors.initials: O
authors.lastname: Zupančič
authors.affiliation: a Department of Pharmaceutical Technology , Institute of Pharmacy, Leopold-Franzens-University Innsbruck , Innsbruck , Austria/Europe and.
authors.forename: Gintare
authors.initials: G
authors.lastname: Leonaviciute
authors.affiliation: a Department of Pharmaceutical Technology , Institute of Pharmacy, Leopold-Franzens-University Innsbruck , Innsbruck , Austria/Europe and.|b Department of Pharmaceutical Technology , Faculty of Pharmacy, Can Tho University of Medicine and Pharmacy , Can Tho City , Vietnam.
authors.forename: Hung Thanh
authors.initials: HT
authors.lastname: Lam
authors.affiliation: a Department of Pharmaceutical Technology , Institute of Pharmacy, Leopold-Franzens-University Innsbruck , Innsbruck , Austria/Europe and.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Partenhauser
authors.affiliation: a Department of Pharmaceutical Technology , Institute of Pharmacy, Leopold-Franzens-University Innsbruck , Innsbruck , Austria/Europe and.
authors.forename: Snežana
authors.initials: S
authors.lastname: Podričnik
authors.affiliation: a Department of Pharmaceutical Technology , Institute of Pharmacy, Leopold-Franzens-University Innsbruck , Innsbruck , Austria/Europe and.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002918:Chymotrypsin / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D045703:Emulsifying Agents / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D005978:Glutathione / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D011092:Polyethylene Glycols / Q000737:chemistry*; D011136:Polysorbates / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry
chemical_list: D045703:Emulsifying Agents; D011136:Polysorbates; D012997:Solvents; C022131:cremophor; D011092:Polyethylene Glycols; D002918:Chymotrypsin; C117608:alpha-chymotrypsin; D005978:Glutathione
keywords: desmopressin; oral peptide delivery; pancreatic lipase; self-emulsifying drug delivery systems; thiol/disulfide exchange reactions; α-chymotrypsin