title: Influence of additives on the properties of nanodroplets formed in highly supersaturated aqueous solutions of ritonavir.
abstract: The formation of colloidal drug aggregates of lipophilic drugs is thought to be of relevance for the oral delivery of poorly water-soluble drugs. In this study, the underlying basis for colloid formation from amorphous solid dispersions and the impact of additives on colloidal stability were evaluated. A relationship was found between the concentration at which colloidal droplets formed upon dissolution of an amorphous solid dispersion and the liquid-liquid phase separation (LLPS) transition concentration, whereby the latter is related to the theoretical amorphous "solubility" value. The composition of the dispersed phase in ritonavir-polymer-water solutions was confirmed to be a noncrystalline, ritonavir-rich droplet phase. Additives were found to impact the size, stability, and crystallization behavior of the colloidal phase. In general, charged additives reduced the kinetics of droplet coalescence, but had a variable effect on crystallization kinetics, either promoting or inhibiting crystallization. Through proper selection of formulation components, it thus appears possible to promote the formation of ∼ 250-350 nm colloidal droplets of ritonavir following dissolution of an amorphous solid dispersion, and to inhibit coalescence and crystallization from these two-phase supersaturated solutions.
authors.affiliation: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana.
authors.forename: Grace A
authors.initials: GA
authors.lastname: Ilevbare
authors.forename: Haoyu
authors.initials: H
authors.lastname: Liu
authors.forename: Junia
authors.initials: J
authors.lastname: Pereira
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Edgar
authors.forename: Lynne S
authors.initials: LS
authors.lastname: Taylor
mesh_terms: D003102:Colloids / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry; D019438:Ritonavir / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D003102:Colloids; D011108:Polymers; D014867:Water; D019438:Ritonavir