title: Continuous manufacturing of delta mannitol by cospray drying with PVP.
abstract: Mannitol is a frequently used diluent in the production of tablets due to its non-hygroscopic character and low drug interaction potential. Although the δ-polymorph of mannitol has superior tabletability in comparison to α- and β-mannitol, the latter are most commonly used because large-scale production of δ-mannitol is difficult. Therefore, a continuous method for production of δ-mannitol was developed in the current study. Spray drying an aqueous solution of mannitol and PVP in a ratio of 4:1 resulted in formation of δ-mannitol. The tabletability of a physical mixture of spray dried δ-mannitol with PVP (5%) and paracetamol (75%) was clearly superior to the tabletability of physical mixtures consisting of spray dried α- and β-mannitol with PVP (5%) and paracetamol (75%) which confirmed the excellent tableting properties of the δ-polymorph. In addition, a coprocessing method was applied to coat paracetamol crystals with δ-mannitol and PVP. The tabletability of the resulting coprocessed particles consisting of 5% PVP, 20% δ-mannitol and 75% paracetamol reached a maximal tensile strength of 2.1 MPa at a main compression pressure of 260 MPa. Moreover the friability of tablets compressed at 184 MPa was only 0.5%. This was attributed to the excellent compression properties of δ-mannitol and the coating of paracetamol crystals with δ-mannitol and PVP during coprocessing.
authors: Laboratory of Pharmaceutical Technology, Ghent University, Belgium.
authors: V
authors: V
authors: Vanhoorne
authors: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Belgium.
authors: P-J
authors: PJ
authors: Van Bockstal
authors: Laboratory of Pharmaceutical Technology, Ghent University, Belgium.
authors: B
authors: B
authors: Van Snick
authors: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Belgium.
authors: E
authors: E
authors: Peeters
authors: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Belgium.
authors: T
authors: T
authors: Monteyne
authors: Laboratory of Nanotechnology, Centro Universitário Franciscano, Santa Maria, Brazil.
authors: P
authors: P
authors: Gomes
authors: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Belgium.
authors: T
authors: T
authors: De Beer
authors: Laboratory of Pharmaceutical Technology, Ghent University, Belgium.
authors: J P
authors: JP
authors: Remon
authors: Laboratory of Pharmaceutical Technology, Ghent University, Belgium. Electronic address: Chris.Vervaet@UGent.be.
authors: C
authors: C
authors: Vervaet
mesh_terms: D000082:Acetaminophen / Q000737:chemistry*; D003890:Desiccation / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D008353:Mannitol / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D013607:Tablets; D013718:Tensile Strength
chemical_list: D013607:Tablets; D000082:Acetaminophen; D008353:Mannitol; D011205:Povidone
keywords: Continuous production; Coprocessing; Delta mannitol; Direct compression; Paracetamol; Particle coating; Spray drying; Tabletability