title: Development of self emulsifying lipid formulations of BCS class II drugs with low to medium lipophilicity.
abstract: Lipid-based formulations can be effective drug delivery systems for poorly water-soluble chemical entities, provided they are designed with careful selection of the excipients, based on their role in the delivery system and in relation to drug properties. The primary factor leading to increased bioavailability is the administration of the drug in a pre-dissolved state thereby avoiding the dissolution limiting step. All model drugs tested (piroxicam, curcumin and nifedipine) belong to the same chemical space--small BCS class II molecules with logP ranging from 2 to 3. These drugs, exhibiting low to medium logP, are not soluble in lipophilic lipid-based excipients (e.g., vegetable oils). Water-soluble and water-dispersible surfactants are able to dissolve the target dose of each drug in the dosage form and efficiently keep it in solution during dispersion. In vitro digestion testing was necessary to discriminate formulations and enable selection of the most robust one. For each molecule, the system with the best performance during dispersion/digestion tests did not comprise the surfactant which delivered the highest solvent capacity for the drug. This study demonstrates the potential of surfactant-based formulations - i.e., Type IV systems from the lipid formulation classification system - for this type of hydrophobic drug.
authors.affiliation: Gattefossé SAS, 36 chemin de Genas 69804 Saint-Priest, France. Electronic address: vjannin@gattefosse.com.
authors.forename: Vincent
authors.initials: V
authors.lastname: Jannin
authors.affiliation: Gattefossé SAS, 36 chemin de Genas 69804 Saint-Priest, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Chevrier
authors.affiliation: Gattefossé SAS, 36 chemin de Genas 69804 Saint-Priest, France; Université Paris-Sud, 5, Rue Jean-Baptiste Clément, 92296 Chatenay-Malabry, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Michenaud
authors.affiliation: Gattefossé SAS, 36 chemin de Genas 69804 Saint-Priest, France; CPE Lyon, University of Lyon, 43 Boulevard du 11 Novembre 1918, 69100 Villeurbanne, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Dumont
authors.affiliation: Gattefossé SAS, 36 chemin de Genas 69804 Saint-Priest, France; University of Parma, Viale G.P. Usberti 27/A 43100 Parma, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Belotti
authors.affiliation: Gattefossé SAS, 36 chemin de Genas 69804 Saint-Priest, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Chavant
authors.affiliation: Gattefossé SAS, 36 chemin de Genas 69804 Saint-Priest, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Demarne
mesh_terms: D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003474:Curcumin / Q000008:administration & dosage; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D005989:Glycerides / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry*; D009543:Nifedipine / Q000008:administration & dosage; D010894:Piroxicam / Q000008:administration & dosage; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D005079:Excipients; D005989:Glycerides; D008055:Lipids; D012997:Solvents; D013501:Surface-Active Agents; D010894:Piroxicam; D009543:Nifedipine; D003474:Curcumin
keywords: Curcumin; Dispersion; Lipolysis; Nifedipine; Piroxicam; Self emulsifying lipid formulations