title: Systematic screening of different surface modifiers for the production of physically stable nanosuspensions.
abstract: The role of a surface modifier is important in the formation of stable nanosuspensions. In this study, a simple and systematic screening method for selecting optimum surface modifiers was performed by utilizing a low-energy wet ball milling method. Nine surface modifiers from different classes with different stabilization mechanisms were applied on six different models of active pharmaceutical ingredients (API). Particle size analysis showed that at concentration five times higher than the critical micelle concentration, SDS and sodium cholate (anionic surfactant) showed the highest percent success to produce stable nanosuspensions with particle size smaller than 250 nm. Similar findings were also shown by poloxamer 188 (nonionic surfactant) and hydroxypropylmethylcellulose E5 (polymeric stabilizer) at concentration 1% (w/v) and 0.8% (w/v), respectively. In addition, combinations of anionic surfactant and nonionic surfactant as well as combinations of anionic surfactant and polymeric stabilizer showed high percent success in the formation of stable nanosuspensions. In general, no correlation can be found between the physicochemical characteristics of the model API (molecular weight, melting point, log P, pKa, and crystallinity) with its feasibility to be nanosized. The concentration and the principle of stabilization of surface modifier determine the formation of stable nanosuspensions.
authors: Institute of Pharmacy, Department of Pharmaceutics, Biopharmaceutics and NutriCosmetics, Freie Universität Berlin, Berlin, Germany; Department of Pharmaceutics, Universitas Airlangga, Surabaya, Indonesia.
authors: Maria L A D
authors: ML
authors: Lestari
authors: Rainer H
authors: RH
authors: Müller
authors: Jan P
authors: JP
authors: Möschwitzer
mesh_terms: D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004355:Drug Stability; D065347:Hypromellose Derivatives / Q000737:chemistry; D008823:Micelles; D008970:Molecular Weight; D053758:Nanoparticles; D036103:Nanotechnology; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry; D020358:Sodium Cholate / Q000737:chemistry; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*; D044366:Transition Temperature
chemical_list: D008823:Micelles; D004364:Pharmaceutical Preparations; D013501:Surface-Active Agents; D020442:Poloxamer; D012967:Sodium Dodecyl Sulfate; D065347:Hypromellose Derivatives; D020358:Sodium Cholate
keywords: critical micelle concentration; nanosuspensions; particle size; physical stability; polymers; screening; stabilization; surface modifier; surfactants; wet ball milling