title: Quality by design: characterization of self-nano-emulsified drug delivery systems (SNEDDs) using ultrasonic resonator technology.
abstract: In the present work, a novel application of ultrasonic measurements is detailed to characterize nano-emulsion formulations as a part of the overall Quality by Design (QbD) goal. Ultrasonic resonator technology (URT) was utilized to measure sound velocity and absorption of self-nanoemulsified drug delivery systems (SNEDDs) consisting of various ratios of oil:surfactant:co-surfactant. A QbD concept was used to create different SNEDDs formulations utilizing sweet orange oil (oil), Emulphor-620 (surfactant), and Capmul (co-surfactant) by dissolving Cyclosporine A in oil. The mixture was emulsified in water and ultrasonic measurements were carried out in an ultrasonic resonator system isothermally for a period of about 15-20min. Compressibility of the individual components in the droplets, hydration of the droplets and the influence of the composition on droplet stability were studied by systematic ultrasonic measurements at a single resonator frequency. The adiabetic compressibilities for the oil, aqueous and interfacial components were 68, 44.6, and 53 [10(-11)Pa(-1)], respectively as calculated using Urick's equation. Also the ultrasonic absorption correlated droplet size of nano-emulsions linearly with R(2) of 0.84 indicating this can be used as an additional technique to measure the droplet size of nano-emulsions. Correlation of ultrasonic data with formulation components indicated that the ultrasonic velocity correlated negatively with increasing oil amount in the formulation as well as surfactant-to-cosurfactant ratios where as droplet diameter correlated positively with these formulation factors. It can be envisioned from the results that the compressibility of the media increases with the addition of the oily component and thus reducing the sound velocity. Thus URT enabled direct and convenient analysis of the physical properties as well as influence of formulation factors of nano-emulsions which is an important indication of stability of these nano-emulsions.
authors.affiliation: Division of Product Quality Research, Office of Testing and Research, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver spring, MD 20993, United States.
authors.forename: R B
authors.initials: RB
authors.lastname: Shah
authors.forename: A S
authors.initials: AS
authors.lastname: Zidan
authors.forename: T
authors.initials: T
authors.lastname: Funck
authors.forename: M A
authors.initials: MA
authors.lastname: Tawakkul
authors.forename: A
authors.initials: A
authors.lastname: Nguyenpho
authors.forename: M A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D000042:Absorption; D002210:Caprylates / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D019245:Compressive Strength; D016572:Cyclosporine / Q000737:chemistry; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D004655:Emulsions; D005989:Glycerides / Q000737:chemistry; D009038:Motion; D053758:Nanoparticles; D010316:Particle Size; D010938:Plant Oils / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*; D014465:Ultrasonics; D014867:Water / Q000737:chemistry*
chemical_list: D002210:Caprylates; D004337:Drug Carriers; D004655:Emulsions; D005989:Glycerides; D010938:Plant Oils; D013501:Surface-Active Agents; D014867:Water; D011092:Polyethylene Glycols; D016572:Cyclosporine; C033084:polyethylene glycol oleyl ether; C087245:orange oil; C025343:monooctanoin