The Use of Glycerol as an Enabling Excipient for Microwave-Induced In Situ Drug Amorphization
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The Use of Glycerol as an Enabling Excipient for Microwave-Induced In Situ Drug Amorphization. / Hempel, Nele-Johanna; Morsch, Flemming; Knopp, Matthias Manne; Berthelsen, Ragna; Lobmann, Korbinian.
In: Journal of Pharmaceutical Sciences, Vol. 110, No. 1, 2021, p. 155-163.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The Use of Glycerol as an Enabling Excipient for Microwave-Induced In Situ Drug Amorphization
AU - Hempel, Nele-Johanna
AU - Morsch, Flemming
AU - Knopp, Matthias Manne
AU - Berthelsen, Ragna
AU - Lobmann, Korbinian
PY - 2021
Y1 - 2021
N2 - Microwave-induced in situ amorphization is a promising approach to circumvent stability and manufacturing issues associated with amorphous solid dispersions (ASD). Using in situ amorphization, the crystalline state of the drug is converted into its amorphous form inside the dosage form, e.g. a compact, upon exposure to microwave radiation. The study aimed to investigate the feasibility of using glycerol as an enabling excipient in compacts prepared from mixtures of indomethacin and Soluplus (R). Additionally, the possibility to form a supersaturated ASD upon exposure to microwave radiation due to elevated temperatures was investigated. It was found that glycerol i) acts as a dielectric heating source absorbing the microwaves, ii) plasticizes the polymer Soluplus (R) and iii) increases the solubility of the drug indomethacin in the polymer Soluplus (R). Additionally, it was found that fully amorphous ASDs could be achieved with drug loadings below -, and slightly above the saturation solubility of indomethacin in the Soluplus (R)/glycerol mixtures, after exposure to 20 min of microwave radiation. Hence, glycerol was a feasible excipient for the microwave-induced in situ amorphization and allowed the preparation of a, at room temperature, supersaturated ASD, due to the elevated temperatures obtained during exposure to microwave radiation. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
AB - Microwave-induced in situ amorphization is a promising approach to circumvent stability and manufacturing issues associated with amorphous solid dispersions (ASD). Using in situ amorphization, the crystalline state of the drug is converted into its amorphous form inside the dosage form, e.g. a compact, upon exposure to microwave radiation. The study aimed to investigate the feasibility of using glycerol as an enabling excipient in compacts prepared from mixtures of indomethacin and Soluplus (R). Additionally, the possibility to form a supersaturated ASD upon exposure to microwave radiation due to elevated temperatures was investigated. It was found that glycerol i) acts as a dielectric heating source absorbing the microwaves, ii) plasticizes the polymer Soluplus (R) and iii) increases the solubility of the drug indomethacin in the polymer Soluplus (R). Additionally, it was found that fully amorphous ASDs could be achieved with drug loadings below -, and slightly above the saturation solubility of indomethacin in the Soluplus (R)/glycerol mixtures, after exposure to 20 min of microwave radiation. Hence, glycerol was a feasible excipient for the microwave-induced in situ amorphization and allowed the preparation of a, at room temperature, supersaturated ASD, due to the elevated temperatures obtained during exposure to microwave radiation. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
KW - Microwave radiation
KW - In situ amorphization
KW - Solubility
KW - Super saturation
KW - Amorphous solid dispersion
KW - AMORPHOUS SOLID DISPERSIONS
KW - HOT-MELT EXTRUSION
KW - DIELECTRIC-PROPERTIES
KW - POLYMER SOLUBILITY
KW - MOLECULAR-WEIGHT
KW - PVP
KW - QUANTIFICATION
KW - PREDICTION
KW - RELEVANT
U2 - 10.1016/j.xphs.2020.10.013
DO - 10.1016/j.xphs.2020.10.013
M3 - Journal article
C2 - 33058897
VL - 110
SP - 155
EP - 163
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
SN - 0022-3549
IS - 1
ER -
ID: 256270143