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 -