title: Nanosuspensions: a promising formulation for the new phospholipase A2 inhibitor PX-18.
abstract: PX-18 is a new highly potent phospholipase A(2) inhibitor with a poor aqueous solubility. Therefore, it was formulated as nanosuspensions with an active content of 1% (w/w), 5% (w/w) and 10% (w/w) using high-pressure homogenization. By contact angle measurements on compressed discs of PX-18, Tween 80 was identified as best wetting agent of PX-18 and therefore used to stabilize the nanosuspensions. The achieved particle size of all nanosuspensions was well in the nanometer range. For the 1% (w/w) PX-18 nanosuspension an average particle size below 50 nm was measured by photon correlation spectroscopy (PCS). A good reproducibility of the mean particle size was found in between different batches. As postulated by the zeta potential of the nanosuspensions, a good physical stability over an observation period of 180 days was obtained when stored at 5+/-3 degrees C. PX-18 formulated as nanosuspensions was chemically stabile. An increase in saturation solubility was found after formulating PX-18 as nanosuspension compared to bulk material, favourable for increasing bioavailability.
authors.affiliation: Department of Pharmaceutics, Biopoharmaceutics and NutriCosmetics, Freie Universität Berlin, Kelchstrasse 31, 12169 Berlin, Germany. jana.pardeike@uni-graz.at
authors.forename: Jana
authors.initials: J
authors.lastname: Pardeike
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Müller
mesh_terms: D017738:Alkanesulfonic Acids / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004337:Drug Carriers / Q000737:chemistry; D004355:Drug Stability; D004356:Drug Storage; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D009829:Oleic Acids / Q000737:chemistry*; D010316:Particle Size; D064801:Phospholipase A2 Inhibitors; D011136:Polysorbates / Q000737:chemistry; D012995:Solubility; D013535:Suspensions / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: C545517:2-(N,N-bis(oleoyloxyethyl)amino)-1-ethanesulfonic acid; D017738:Alkanesulfonic Acids; D004337:Drug Carriers; D009829:Oleic Acids; D064801:Phospholipase A2 Inhibitors; D011136:Polysorbates; D013535:Suspensions