Hempel Nele-Johanna, Merkl Padryk, Knopp Matthias Manne, Berthelsen Ragna, Teleki Alexandra, Sotiriou Georgios A, Löbmann Korbinian
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17177 Stockholm, Sweden.
Pharmaceutics. 2021 Jun 21;13(6):917. doi: 10.3390/pharmaceutics13060917.
In this study, laser-induced in situ amorphization (i.e., amorphization inside the final dosage form) of the model drug celecoxib (CCX) with six different polymers was investigated. The drug-polymer combinations were studied with regard to the influence of (i) the physicochemical properties of the polymer, e.g., the glass transition temperature () and (ii) the drug-polymer solubility on the rate and degree of in situ drug amorphization. Compacts were prepared containing 30 wt% CCX, 69.25 wt% polymer, 0.5 wt% lubricant, and 0.25 wt% plasmonic nanoparticles (PNs) and exposed to near-infrared laser radiation. Upon exposure to laser radiation, the PNs generated heat, which allowed drug dissolution into the polymer at temperatures above its , yielding an amorphous solid dispersion. It was found that in situ drug amorphization was possible for drug-polymer combinations, where the temperature reached during exposure to laser radiation was above the onset temperature for a dissolution process of the drug into the polymer, i.e., . The findings of this study showed that the concept of laser-induced in situ drug amorphization is applicable to a range of polymers if the drug is soluble in the polymer and temperatures during the process are above .
在本研究中，研究了模型药物塞来昔布（CCX）与六种不同聚合物的激光诱导原位非晶化（即在最终剂型内部进行非晶化）。研究了药物 - 聚合物组合在以下方面的影响：（i）聚合物的物理化学性质，例如玻璃化转变温度（），以及（ii）药物 - 聚合物溶解度对原位药物非晶化的速率和程度的影响。制备了含有30 wt% CCX、69.25 wt%聚合物、0.5 wt%润滑剂和0.25 wt%等离子体纳米颗粒（PNs）的压片，并使其暴露于近红外激光辐射下。在暴露于激光辐射时，PNs产生热量，这使得药物在高于其的温度下溶解到聚合物中，从而产生无定形固体分散体。研究发现，对于药物 - 聚合物组合，当暴露于激光辐射期间达到的温度高于药物溶解到聚合物的溶解过程的起始温度，即 时，原位药物非晶化是可能的。本研究结果表明，如果药物可溶于聚合物且过程中的温度高于 ，激光诱导原位药物非晶化的概念适用于一系列聚合物。
