Department of Pharmacy, University of Copenhagen, 2100 Copenhagen, Denmark.
Bioneer:FARMA, Department of Pharmacy, 2100 Copenhagen, Denmark.
J Pharm Sci. 2021 Jan;110(1):155-163. doi: 10.1016/j.xphs.2020.10.013. Epub 2020 Oct 13.
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®. 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® and iii) increases the solubility of the drug indomethacin in the polymer Soluplus®. 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®/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.
微波诱导原位非晶化是一种有前途的方法，可以规避与无定形固体分散体（ASD）相关的稳定性和制造问题。通过原位非晶化，药物的晶态在暴露于微波辐射时在剂型内（例如，在致密体内）转化为无定形态。本研究旨在探讨甘油作为赋形剂在吲哚美辛和 Soluplus®混合物制备的片剂中的应用可行性。此外，还研究了由于温度升高而在暴露于微波辐射时形成过饱和 ASD 的可能性。结果发现，甘油 i）作为介电加热源吸收微波，ii）使聚合物 Soluplus®增塑，iii）增加了药物吲哚美辛在聚合物 Soluplus®中的溶解度。此外，还发现，在暴露于微波辐射 20 分钟后，完全无定形 ASD 可以在低于和略高于吲哚美辛在 Soluplus®/甘油混合物中的饱和溶解度的载药量下实现。因此，甘油是微波诱导原位非晶化的一种可行的赋形剂，由于在暴露于微波辐射期间获得的高温，允许制备室温下的过饱和 ASD。
