title: Excipient selection can significantly affect solid-state phase transformation in formulation during wet granulation.
abstract: Phase transformations in formulations can lead to instability in physicochemical, biopharmaceutical, and processing properties of products. The influences of formulation design on the optimal dosage forms should be specified. The aim here was to investigate whether excipients with different water sorption behavior affect hydrate formation of nitrofurantoin in wet masses. Nitrofurantoin anhydrate was used as a hydrate-forming model drug, and 4 excipients with different water-absorbing potential (amorphous low-substituted hydroxypropylcellulose, modified maize starch, partially amorphous silicified microcrystalline cellulose, and crystalline alpha-lactose monohydrate) were granulated with varying amounts of purified water. Off-line evaluation of wet masses containing nitrofurantoin anhydrate and excipient (1:1) was performed using an X-ray powder diffractometer (XRPD) and near-infrared spectroscopy, and drying phase was evaluated by variable temperature XRPD. Only amorphous excipient in the formulation retarded hydrate formation of an active pharmaceutical ingredient (API) at high water contents. Hygroscopic partially crystalline excipient hindered hydrate formation of API at low water contents. Crystalline excipient was unable to control hydrate formation of API. The character of excipient affects the stability of formulation. Thus, correct selection of excipients for the formulation can control processing-induced phase transitions and improve the storage stability of the final dosage form.
authors.affiliation: Pharmaceutical Technology Division, Faculty of Pharmacy, FIN-00014 University of Helsinki, Helsinki, Finland. sari.airaksinen@helsinki.fi
authors.forename: Sari
authors.initials: S
authors.lastname: Airaksinen
authors.forename: Milja
authors.initials: M
authors.lastname: Karjalainen
authors.forename: Niina
authors.initials: N
authors.lastname: Kivikero
authors.forename: Sari
authors.initials: S
authors.lastname: Westermarck
authors.forename: Anna
authors.initials: A
authors.lastname: Shevchenko
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
authors.forename: Jouko
authors.initials: J
authors.lastname: Yliruusi
mesh_terms: D002626:Chemistry, Pharmaceutical; D005079:Excipients / Q000032:analysis / Q000138:chemical synthesis*; D044367:Phase Transition; D017155:Wettability
chemical_list: D005079:Excipients