title: The influence of cetomacrogol ointment processing on structure: A definitive screening design.
abstract: Batch-to-batch variability is a challenge for the industrial scale production of ointments. Therefore the current investigation focussed on identifying and understanding critical process parameters (CPPs) for cetomacrogol ointment. This was evaluated using a definitive screening design (DSD) approach in which fourteen batches were produced under predefined and controlled conditions using the following variables: addition of SiO2nanoparticles, mixing speed, cooling rate, heating temperature, container filling temperature and isothermal mixing at the filling temperature. Ointment structure was evaluated using a number of rheological parameters. One of these parameters, yield stress was found to be strongly influenced by filling temperature and mixing speed (p=0.0065 and p=0.0013 respectively). Both significantly affect ointment structure and they also have a significant interaction (p<0.05). Understanding the ointment production process can help in defining a processing window to produce ointment of constant quality.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands; Research and Development Department, Tiofarma B.V., Hermanus Boerhaavestraat 1, 3261 ME, Oud-Beijerland, The Netherlands. Electronic address: tvheugten@tiofarma.nl.
authors.forename: A J P
authors.initials: AJ
authors.lastname: van Heugten
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands; Research and Development Department, Tiofarma B.V., Hermanus Boerhaavestraat 1, 3261 ME, Oud-Beijerland, The Netherlands.
authors.forename: C L
authors.initials: CL
authors.lastname: Braal
authors.affiliation: Department of Inorganic Chemistry and Catalysis, Debye Institute for Nanomaterials Science, Utrecht University, 3584 CG Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Versluijs-Helder
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands; Research and Development Department, Tiofarma B.V., Hermanus Boerhaavestraat 1, 3261 ME, Oud-Beijerland, The Netherlands; Department of Clinical Pharmacy, Division of Laboratory Medicine & Pharmacy, University Medical Centre Utrecht, P/O Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Vromans
mesh_terms: D002592:Cetomacrogol / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry; D009824:Ointments / Q000737:chemistry*; D011786:Quality Control; D012822:Silicon Dioxide / Q000737:chemistry; D013696:Temperature
chemical_list: D009824:Ointments; D012822:Silicon Dioxide; D002592:Cetomacrogol
keywords: Critical process parameters (CPPs); Definitive screening design (DSD); Design of experiments (DoE); Ointment; Quality by design (QbD); Rheology