title: A systematic dilution study of self-microemulsifying drug delivery systems in artificial intestinal fluid using dynamic laser light backscattering.
abstract: Self-microemulsifying drug delivery systems provide a key technology to formulate poorly soluble drugs. The development of candidate formulations is commonly based on a screening of in vitro dilution characteristics. Because in vitro dilution is conducted in many different ways, the comparability of data is often limited and the involved factors are not properly understood. This article aims to systematically study the impact of formulation factors, temperature, dilution medium, and its amount in view of the phase behavior and particle size. Three types of self-microemulsifying delivery vehicles were formulated and diluted in artificial intestinal fluid and water. Different testing conditions were studied in the framework of statistical designs. The main response parameter was the colloidal particle size, which was measured using dynamic laser light backscattering. The tested formulations resulted in swollen micelles at a high dilution of 1:100 up to 1:1,000. At a lower dilution of 1:10, the particle size was increased depending on the system. Interactions of the dilution level with other parameters were found significant. Based on the obtained results, it seems reasonable to screen such systems first at a higher dilution in water at room temperature to facilitate experimentation. The selected systems may then, in a second step, be further studied at a different lower dilution in water or in artificial intestinal fluid at 37 degrees C. We found that the Cremophor formulations were particularly robust with respect to producing constant small particles at different dilution levels. More research is needed to explore the biopharmaceutical relevance of these in vitro findings.
authors.affiliation: Institute of Pharmaceutical Technology, University of Basel, Basel, Switzerland.
authors.forename: Celine
authors.initials: C
authors.lastname: Ditner
authors.forename: Roberto
authors.initials: R
authors.lastname: Bravo
authors.forename: Georgios
authors.initials: G
authors.lastname: Imanidis
authors.forename: Martin
authors.initials: M
authors.lastname: Kuentz
mesh_terms: D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D045703:Emulsifying Agents / Q000737:chemistry*; D004655:Emulsions; D007408:Intestinal Absorption; D007834:Lasers; D008027:Light; D008567:Membranes, Artificial; D008823:Micelles; D009391:Nephelometry and Turbidimetry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D012542:Scattering, Radiation; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013696:Temperature
chemical_list: D045703:Emulsifying Agents; D004655:Emulsions; D008567:Membranes, Artificial; D008823:Micelles; D013501:Surface-Active Agents; C022131:cremophor; D011092:Polyethylene Glycols