title: Solid lipid particles for oral delivery of peptide and protein drugs III - the effect of fed state conditions on the in vitro release and degradation of desmopressin.
abstract: The effect of food intake on the release and degradation of peptide drugs from solid lipid particles is unknown and was therefore investigated in vitro using different fed state media in a lipolysis model. Desmopressin was used as a model peptide and incorporated into solid lipid particles consisting of trimyristin (TG14), tripalmitin (TG16), and tristearin (TG18), respectively. Fasted state and fed state media with varying phospholipid and bile salt concentrations, as well as fed state media with milk and oleic acid glycerides, respectively, were used as the release media. The presence of oleic acid glycerides accelerated the release of desmopressin significantly from all solid lipid particles both in the presence and absence of lipase. The presence of oleic acid glycerides also reduced the degradation rate of desmopressin, probably due to the interactions between the lipids and the protease or desmopressin. Addition of a medium chain triglyceride, trilaurin, in combination with drug-loaded lipid particles diminished the food effect on the TG18 particles, and trilaurin is therefore proposed to be a suitable excipient for reduction of the food effect. Overall, the present study shows that strategies to reduce food effect, such as adding trilaurin, for lipid particle formulations should be considered as drug release from such formulations might be influenced by the presence of food in the gastrointestinal tract.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen, Denmark.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Christophersen
authors.forename: Dimple
authors.initials: D
authors.lastname: Vaghela
authors.forename: Anette
authors.initials: A
authors.lastname: Müllertz
authors.forename: Mingshi
authors.initials: M
authors.lastname: Yang
authors.forename: Hanne M
authors.initials: HM
authors.lastname: Nielsen
authors.forename: Huiling
authors.initials: H
authors.lastname: Mu
mesh_terms: D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D004435:Eating; D005079:Excipients; D005215:Fasting / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry; D018565:Food-Drug Interactions; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry; D008049:Lipase / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008066:Lipolysis; D019301:Oleic Acid / Q000737:chemistry; D010455:Peptides / Q000008:administration & dosage*; D011506:Proteins / Q000008:administration & dosage*
chemical_list: D005079:Excipients; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D008055:Lipids; D010455:Peptides; D011506:Proteins; D019301:Oleic Acid; D008049:Lipase; D003894:Deamino Arginine Vasopressin