title: Engineering of nano-crystalline drug suspensions: employing a physico-chemistry based stabilizer selection methodology or approach.
abstract: This paper describes a systematic approach to select optimum stabilizer for the preparation of nano-crystalline suspensions of an active pharmaceutical ingredient (API). The stabilizer can be either a dispersant or a combination of dispersant and wetting agent. The proposed screening method is a quick and efficient way to investigate a large number of stabilizers based on the principles of physical-chemistry and employs a stepwise approach. The methodology has been divided in two main parts; the first part being focused on the qualitative screening with the objective of selecting the best candidate(s) for further investigation, the second part has been focused on quantitative screening with the objective to optimize the ratio and amount of wetting and dispersing agents, based on wettability, surface charges measurement, adsorption evaluation, process-ability evaluation and storage stability. The results showed clearly that SDS/PVP 40/60% (w/w) (sodium dodecyl sulfate/poly(vinyl pyrrolidone)) at a total concentration of 1.2% was the optimum stabilizer composition, at which the resulting nanosuspensions were stable for more than 50 days at room temperature.
authors.affiliation: Sanofi R&D, 13, quai Jules Guesde, Vitry sur Seine 94403, France. Electronic address: mostafa.nakach@sanofi.com.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Nakach
authors.affiliation: Sanofi R&D, 13, quai Jules Guesde, Vitry sur Seine 94403, France. Electronic address: Jean-Rene.Authelin@sanofi.com.
authors.forename: Jean-René
authors.initials: JR
authors.lastname: Authelin
authors.affiliation: 89 Nash Grove Lane, Wokingham, Berkshire RG40 4HE, UK. Electronic address: tharwat@tadros.fsnet.co.uk.
authors.forename: Tharwat
authors.initials: T
authors.lastname: Tadros
authors.affiliation: Ecole des Mines d'Albi, Campus Jarlard, Route de Teillet 83013, France. Electronic address: laurence.Galet@mines-albi.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Galet
authors.affiliation: Ecole des Mines d'Albi, Campus Jarlard, Route de Teillet 83013, France. Electronic address: alain.chamayou@mines-albi.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Chamayou
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D053758:Nanoparticles; D011205:Povidone / Q000737:chemistry*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry*; D013535:Suspensions; D013696:Temperature; D013997:Time Factors; D017155:Wettability
chemical_list: D005079:Excipients; D013535:Suspensions; D012967:Sodium Dodecyl Sulfate; D011205:Povidone
keywords: Beads milling; Dispersant agent; Nano-crystalline suspension; Stabilizer; Top down process; Wetting agent