title: Toward the establishment of standardized in vitro tests for lipid-based formulations, part 4: proposing a new lipid formulation performance classification system.
abstract: The Lipid Formulation Classification System Consortium looks to develop standardized in vitro tests and to generate much-needed performance criteria for lipid-based formulations (LBFs). This article highlights the value of performing a second, more stressful digestion test to identify LBFs near a performance threshold and to facilitate lead formulation selection in instances where several LBF prototypes perform adequately under standard digestion conditions (but where further discrimination is necessary). Stressed digestion tests can be designed based on an understanding of the factors that affect LBF performance, including the degree of supersaturation generated on dispersion/digestion. Stresses evaluated included decreasing LBF concentration (↓LBF), increasing bile salt, and decreasing pH. Their capacity to stress LBFs was dependent on LBF composition and drug type: ↓LBF was a stressor to medium-chain glyceride-rich LBFs, but not more hydrophilic surfactant-rich LBFs, whereas decreasing pH stressed tolfenamic acid LBFs, but not fenofibrate LBFs. Lastly, a new Performance Classification System, that is, LBF composition independent, is proposed to promote standardized LBF comparisons, encourage robust LBF development, and facilitate dialogue with the regulatory authorities. This classification system is based on the concept that performance evaluations across three in vitro tests, designed to subject a LBF to progressively more challenging conditions, will enable effective LBF discrimination and performance grading.
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052, Australia; Capsugel R&D, Strasbourg, France.
authors.forename: Hywel D
authors.initials: HD
authors.lastname: Williams
authors.forename: Philip
authors.initials: P
authors.lastname: Sassene
authors.forename: Karen
authors.initials: K
authors.lastname: Kleberg
authors.forename: Marilyn
authors.initials: M
authors.lastname: Calderone
authors.forename: Annabel
authors.initials: A
authors.lastname: Igonin
authors.forename: Eduardo
authors.initials: E
authors.lastname: Jule
authors.forename: Jan
authors.initials: J
authors.lastname: Vertommen
authors.forename: Ross
authors.initials: R
authors.lastname: Blundell
authors.forename: Hassan
authors.initials: H
authors.lastname: Benameur
authors.forename: Anette
authors.initials: A
authors.lastname: Müllertz
authors.forename: Christopher J H
authors.initials: CJ
authors.lastname: Porter
authors.forename: Colin W
authors.initials: CW
authors.lastname: Pouton
mesh_terms: D000700:Analgesics / Q000737:chemistry; D001647:Bile Acids and Salts / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D011345:Fenofibrate / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D000960:Hypolipidemic Agents / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D062367:ortho-Aminobenzoates / Q000737:chemistry
chemical_list: D000700:Analgesics; D001647:Bile Acids and Salts; D005079:Excipients; D000960:Hypolipidemic Agents; D008055:Lipids; D004364:Pharmaceutical Preparations; D013501:Surface-Active Agents; D062367:ortho-Aminobenzoates; C009500:tolfenamic acid; D011345:Fenofibrate
keywords: LFCS Consortium; SEDDS; bioavailability; drug solubilization; in vitro digestion testing; in vitro models; lipid-based drug delivery systems; precipitation; solubility; supersaturation