TY - JOUR

T1 - Microwave-Induced in Situ Drug Amorphization Using a Mixture of Polyethylene Glycol and Polyvinylpyrrolidone

AU - Hempel, Nele Johanna

AU - Knopp, Matthias M.

AU - Zeitler, J. Axel

AU - Berthelsen, Ragna

AU - Löbmann, Korbinian

N1 - Publisher Copyright: © 2021 The Authors

PY - 2021

Y1 - 2021

N2 - The use of a mixture of polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP) was investigated for microwave-induced in situ amorphization of celecoxib (CCX) inside compacts. Such amorphization requires the presence of a dipolar excipient in the formulation to ensure heating of the compact by absorption of the microwaves. Previously, the hygroscopic nature of PVP was exploited for this purpose. By exposing PVP-based compacts for set time intervals at defined relative humidity, controlled water sorption into the compacts was achieved. In the present study, PEG was proposed as the microwave absorbing excipient instead of water, to avoid the water sorption step. However, it was found that PEG alone melted upon exposure to microwave radiation and caused the compact to deform. Furthermore, CCX was found to recrystallize upon cooling in PEG-based formulations. Hence, a mixture of PEG and PVP was used, where the presence of PVP preserved the physical shape of the compact, and the physical state of the amorphous solid dispersion. To study the impact of the polymer mixture, different compact compositions of CCX, PEG and PVP were prepared. When exposing the compacts to microwave radiation, it was found that the PEG:PVP ratio was critical for in situ amorphization and that complete amorphization was only achieved above a certain temperature threshold.

AB - The use of a mixture of polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP) was investigated for microwave-induced in situ amorphization of celecoxib (CCX) inside compacts. Such amorphization requires the presence of a dipolar excipient in the formulation to ensure heating of the compact by absorption of the microwaves. Previously, the hygroscopic nature of PVP was exploited for this purpose. By exposing PVP-based compacts for set time intervals at defined relative humidity, controlled water sorption into the compacts was achieved. In the present study, PEG was proposed as the microwave absorbing excipient instead of water, to avoid the water sorption step. However, it was found that PEG alone melted upon exposure to microwave radiation and caused the compact to deform. Furthermore, CCX was found to recrystallize upon cooling in PEG-based formulations. Hence, a mixture of PEG and PVP was used, where the presence of PVP preserved the physical shape of the compact, and the physical state of the amorphous solid dispersion. To study the impact of the polymer mixture, different compact compositions of CCX, PEG and PVP were prepared. When exposing the compacts to microwave radiation, it was found that the PEG:PVP ratio was critical for in situ amorphization and that complete amorphization was only achieved above a certain temperature threshold.

KW - Amorphous solid dispersion

KW - Drug loading

KW - In situ amorphization

KW - Microwave irradiation

KW - Polyethylene glycol

KW - Ternary phase diagram

KW - Transmission Raman spectroscopy

U2 - 10.1016/j.xphs.2021.05.010

DO - 10.1016/j.xphs.2021.05.010

M3 - Journal article

C2 - 34022194

AN - SCOPUS:85108570176

VL - 110

SP - 3221

EP - 3229

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 9

ER -