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

• Main Authors: Nele-Johanna Hempel (Author), Padryk Merkl (Author), Matthias Manne Knopp (Author), Ragna Berthelsen (Author), Alexandra Teleki (Author), Georgios A. Sotiriou (Author), Korbinian Löbmann (Author)
• Formato: Livro
• Publicado em: MDPI AG, 2021-06-01T00:00:00Z.
• Assuntos: article
• Acesso em linha: Connect to this object online.
• Notes: 10.3390/pharmaceutics13060917; 1999-4923
• Keywords: oral drug delivery; in situ drug amorphization; polymers; amorphous solid dispersion; laser radiation; plasmonic nanoparticles; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 13, Iss 6, p 917 (2021)

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 (<i>T</i>_g) 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 <i>T</i>_g, 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., <i>T</i>_DStart. 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 <i>T</i>_DStart.