title: Amorphization within the tablet: Using microwave irradiation to form a glass solution in situ.
abstract: In situ amorphization is a concept that allows to amorphize a given drug in its final dosage form right before administration. Hence, this approach can potentially be used to circumvent recrystallization issues that other amorphous formulation approaches are facing during storage. In this study, the feasibility of microwave irradiation to prepare amorphous solid dispersions (glass solutions) in situ was investigated. Indomethacin (IND) and polyvinylpyrrolidone K12 (PVP) were tableted at a 1:2 (w/w) ratio. In order to study the influence of moisture content and energy input on the degree of amorphization, tablet formulations were stored at different relative humidity (32, 43 and 54% RH) and subsequently microwaved using nine different power-time combinations up to a maximum energy input of 90kJ. XRPD results showed that up to 80% (w/w) of IND could be amorphized within the tablet. mDSC measurements revealed that with increasing microwaving power and time, the fractions of crystalline IND and amorphous PVP reduced, whereas the amount of in situ formed IND-PVP glass solution increased. Intrinsic dissolution showed that the dissolution rate of the microwaved solid dispersion was similar to that of a quench cooled, fully amorphous glass solution even though the microwaved samples contained residual crystalline IND.
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. Electronic address: maria.doreth@sund.ku.dk.
authors.forename: Maria
authors.initials: M
authors.lastname: Doreth
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. Electronic address: szm610@alumni.ku.dk.
authors.forename: Murtadha Abdul
authors.initials: MA
authors.lastname: Hussein
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. Electronic address: petra.priemel@sund.ku.dk.
authors.forename: Petra A
authors.initials: PA
authors.lastname: Priemel
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. Electronic address: holger.grohganz@sund.ku.dk.
authors.forename: Holger
authors.initials: H
authors.lastname: Grohganz
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark; Drug Product Development, Janssen Research and Development, Johnson & Johnson, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: rholm@ITS.JNJ.com.
authors.forename: René
authors.initials: R
authors.lastname: Holm
authors.affiliation: Analytical Development & Compliance, H. Lundbeck A/S, Ottiliavej 9, 2500 Valby, Denmark. Electronic address: hld@lundbeck.com.
authors.forename: Heidi
authors.initials: H
authors.lastname: Lopez de Diego
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. Electronic address: thomas.rades@sund.ku.dk.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. Electronic address: korbinian.loebmann@sund.ku.dk.
authors.forename: Korbinian
authors.initials: K
authors.lastname: Löbmann
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry; D004355:Drug Stability; D005898:Glass / Q000737:chemistry*; D006813:Humidity; D007213:Indomethacin / Q000737:chemistry; D008872:Microwaves; D019999:Pharmaceutical Solutions / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D012995:Solubility; D013607:Tablets / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D019999:Pharmaceutical Solutions; D011145:Polyvinyls; D011759:Pyrrolidines; D013607:Tablets; C505150:poly(N-vinylpyrrolidine); D007213:Indomethacin
keywords: Amorphization; Glass solution; In situ; Microwave radiation; Recrystallization; Tablet