TY - JOUR

T1 - The Influence of Drug-Polymer Solubility on Laser-Induced In Situ Drug Amorphization Using Photothermal Plasmonic Nanoparticles

AU - Hempel, Nele-Johanna

AU - Merkl, Padryk

AU - Knopp, Matthias Manne

AU - Berthelsen, Ragna

AU - Teleki, Alexandra

AU - Sotiriou, Georgios A.

AU - Lobmann, Korbinian

PY - 2021

Y1 - 2021

N2 - 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 (Tg) 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 Tg, 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., TDStart. 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 TDStart.

AB - 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 (Tg) 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 Tg, 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., TDStart. 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 TDStart.

KW - oral drug delivery

KW - in situ drug amorphization

KW - polymers

KW - amorphous solid dispersion

KW - laser radiation

KW - plasmonic nanoparticles

KW - pharmaceutical nanotechnology

U2 - 10.3390/pharmaceutics13060917

DO - 10.3390/pharmaceutics13060917

M3 - Journal article

C2 - 34205754

VL - 13

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 6

M1 - 917

ER -