Utilizing Laser Activation of Photothermal Plasmonic Nanoparticles to Induce On-Demand Drug Amorphization inside a Tablet

Abstract

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-2 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.

The Influence of Drug–Polymer Solubility on Laser-Induced In Situ Drug Amorphization Using Photothermal Plasmonic Nanoparticles

“…Successful in situ drug amorphization has previously been described by various methods, such as water immersion [ 8 ] and the use of microwave radiation [ 1 , 2 , 3 , 4 , 5 , 9 ] and laser radiation [ 10 ]. The latter two methods utilize electromagnetic radiation sources and were reported to lead to complete amorphization of a compact containing 30 wt% celecoxib (CCX) and the polymer polyvinylpyrrolidone (PVP12) within relatively short time periods, i.e., 10 min of exposure to microwave radiation [ 2 ] and 3 min of exposure to laser radiation [ 10 ].…”

“…With the concept of laser-induced in situ drug amorphization, it is possible to reduce the amount of enabling excipient needed inside the compact, as well as the total exposure time. Furthermore, higher temperatures (up to 150 °C) upon exposure have been reached compared to the use of microwave radiation [ 10 ], which can potentially enable the amorphization of more drug–polymer combinations. Using laser radiation, heating of the compacts is achieved by introducing silver plasmonic nanoparticles (PNs), which absorb laser radiation in the near-infrared (near-IR) spectrum.…”

“…In this study, the silver PNs were obtained by flame spray pyrolysis (FSP) [ 16 , 17 , 18 ]. Using PNs at 0.1 wt% or 0.25 wt%, laser-induced in situ drug amorphization was successfully obtained for CCX in combination with PVP12 [ 10 ]. In the before-mentioned study, it was shown that increasing laser intensity as well as increasing PN load led to a faster temperature increase and a higher maximum temperature, resulting in a faster rate and higher degree of amorphization [ 10 ].…”

“…Using PNs at 0.1 wt% or 0.25 wt%, laser-induced in situ drug amorphization was successfully obtained for CCX in combination with PVP12 [ 10 ]. In the before-mentioned study, it was shown that increasing laser intensity as well as increasing PN load led to a faster temperature increase and a higher maximum temperature, resulting in a faster rate and higher degree of amorphization [ 10 ]. This proof-of-concept study was, however, limited to a single polymer, namely PVP12, which has also been successfully amorphized using microwave radiation [ 2 , 9 , 10 ].…”

“…In the before-mentioned study, it was shown that increasing laser intensity as well as increasing PN load led to a faster temperature increase and a higher maximum temperature, resulting in a faster rate and higher degree of amorphization [ 10 ]. This proof-of-concept study was, however, limited to a single polymer, namely PVP12, which has also been successfully amorphized using microwave radiation [ 2 , 9 , 10 ]. Compacts exposed to laser radiation became fully amorphous after only 3 min compared to exposure to microwave radiation, for which 10 min of exposure was needed to achieve complete amorphization.…”