Department of Pharmacy, University of Copenhagen, 2100 Copenhagen, Denmark.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17177 Stockholm, Sweden.
Mol Pharm. 2021 Jun 7;18(6):2254-2262. doi: 10.1021/acs.molpharmaceut.1c00077. Epub 2021 May 5.
Poor aqueous drug solubility represents a major challenge in oral drug delivery. A novel approach to overcome this challenge is drug amorphization inside a tablet, that is, on-demand drug amorphization. The amorphous form is a thermodynamically instable, disordered solid-state with increased dissolution rate and solubility compared to its crystalline counterpart. During on-demand drug amorphization, the drug molecularly disperses into a polymer to form an amorphous solid at elevated temperatures inside a tablet. This study investigates, for the first time, the utilization of photothermal plasmonic nanoparticles for on-demand drug amorphization as a new pharmaceutical application. For this, near-IR photothermal plasmonic nanoparticles were tableted together with a crystalline drug (celecoxib) and a polymer (polyvinylpyrrolidone). The tablets were subjected to a near-IR laser at different intensities and durations to study the rate of drug amorphization under each condition. During laser irradiation, the plasmonic nanoparticles homogeneously heated the tablet. The temperature was directly related to the rate and degree of amorphization. Exposure times as low as 180 s at 1.12 W cm laser intensity with only 0.25 wt % plasmonic nanoparticles and up to 50 wt % drug load resulted in complete drug amorphization. Therefore, near-IR photothermal plasmonic nanoparticles are promising excipients for on-demand drug amorphization with laser irradiation.
药物水溶性差是口服药物递送的主要挑战。克服这一挑战的一种新方法是在片剂内部使药物非晶化，即按需药物非晶化。无定形形式是一种热力学不稳定的无序固态，与晶型相比，其溶解速率和溶解度增加。在按需药物非晶化过程中，药物在高温下分子分散在聚合物中，在片剂内部形成无定形固体。本研究首次探讨了光热等离子体纳米粒子在按需药物非晶化中的应用，将其作为一种新的药物应用。为此，将近红外光热等离子体纳米粒子与一种晶态药物（塞来昔布）和一种聚合物（聚乙烯吡咯烷酮）压制成片剂。将片剂在不同强度和时间的近红外激光下进行照射，以研究每种条件下药物非晶化的速率。在激光照射下，等离子体纳米粒子均匀地加热片剂。温度与非晶化的速率和程度直接相关。在 1.12 W cm 的激光强度下，仅需 0.25wt%的等离子体纳米粒子，照射 180 秒，药物负载量高达 50wt%，即可实现药物完全非晶化。因此，近红外光热等离子体纳米粒子是具有激光照射的按需药物非晶化有前途的赋形剂。
