Microwave-induced in situ drug amorphization using a mixture of polyethylene glycol and polyvinylpyrrolidone
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.
Download the full article here (journal pre-proof): Microwave-induced in situ drug amorphization using a mixture of polyethylene glycol and polyvinylpyrrolidone
or continue reading here: Nele-Johanna Hempel, Matthias M. Knopp, J. Axel Zeitler, Ragna Berthelsen, Korbinian Löbmann, Microwave-induced in situ drug amorphization using a mixture of polyethylene glycol and polyvinylpyrrolidone,
Journal of Pharmaceutical Sciences, 2021, ISSN 0022-3549, https://doi.org/10.1016/j.xphs.2021.05.010. (https://www.sciencedirect.com/science/article/pii/S0022354921002549)
Celecoxib (CCX, Mw= 381.37 g/mol) and magnesium stearate (MgSt, Mw = 591.27 g/mol) were purchased from Fagron Nordic A/S (Copenhagen, Denmark). Polyethylene glycol (PEG) 2000 (Mw = 2000 g/mol) and PEG 3000 (Mw = 3000 g/mol) were a kind gift from Merck KGaA (Darmstadt, Germany). PEG 4000 (Mw = 4000 g/mol) was purchased from Honeywell Fluka (Vallensbæk, Denmark). Kollidon® 17PF (PVP, Mw= 7000-11000 g/mol) was kindly gifted by BASF (Ludwigshafen, Germany). Silica gel was purchased from Sigma-Aldrich A/S (St. Louis, MO, USA). All chemicals were used as received.
The influence of a mixture of PEG and PVP on the microwaved-induced in situ amorphization was studied using PEG 2000 and PEG 3000, and drug loadings of 30 wt% and 50 wt%. A polymeric blend of PEG and PVP in the compact was found favorable for the formation of a completely amorphous ASD to (i) allow sufficient dielectric heating by the polymer PEG and (ii) maintain the physical shape of the compact by PVP and (iii) hinder recrystallization of the obtained ASD upon cooling by PVP. Using compacts containing mixtures of PVP and PEG, completely amorphous solid dispersions were obtained after 600 s of exposure to microwave radiation. Compacts containing PEG 2000 showed a slightly faster rate of amorphization than compacts with PEG 3000. Overall, the use of a mixture of PEG and PVP was found superior over the use of the individual polymers and suitable for in situ amorphization with a drug load of up to 50 wt%, which is the highest, so far reported.