title: Efficient production of nanoparticle-loaded orodispersible films by process integration in a stirred media mill.
abstract: Orodispersible films possess a great potential as a versatile platform for nanoparticle-loaded oral dosage forms. In this case, poorly water-soluble organic materials were ground in a stirred media mill and embedded into a polymer matrix. The aim of this study was the shortening of this manufacturing process by the integration of several process steps into a stirred media mill without facing disadvantages regarding the film quality. Furthermore, this process integration is time conserving due to the high stress intensities provided in the mill and applicable for high solids contents and high suspension viscosities. Two organic materials, the model compound Anthraquinone and the active pharmaceutical ingredient Naproxen were investigated in this study. Besides the impact of the film processing on the crystallinity of the particles in the orodispersible film, a particle load of up to 50% was investigated with the new developed processing route. Additionally, a disintegration test was developed, combining an appropriate amount of saliva substitute and a clear endpoint determination. In summary, high nanoparticle loads in orodispersible films with good particle size preservation after film redispersion in water as well as a manufacturing of the film casting mass within a few minutes in a stirred media mill was achieved.
authors.affiliation: Institute for Particle Technology, Technische Universität Braunschweig, PVZ-Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Germany. Electronic address: d.steiner@tu-braunschweig.de.
authors.forename: Denise
authors.initials: D
authors.lastname: Steiner
authors.affiliation: Institute for Particle Technology, Technische Universität Braunschweig, PVZ-Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Germany.
authors.forename: Jan Henrik
authors.initials: JH
authors.lastname: Finke
authors.affiliation: Institute for Particle Technology, Technische Universität Braunschweig, PVZ-Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Kwade
mesh_terms: D000284:Administration, Oral; D000880:Anthraquinones / Q000737:chemistry / Q000493:pharmacokinetics*; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D053758:Nanoparticles / Q000737:chemistry*; D009288:Naproxen / Q000737:chemistry / Q000493:pharmacokinetics*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*
chemical_list: D000880:Anthraquinones; D011108:Polymers; D009288:Naproxen
keywords: Disintegration method; Nanoparticle-loaded ODFs; Orodispersible film; Process integration; SFaB tester; Stirred media mill