Journal
PHARMACEUTICS
Volume 13, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/pharmaceutics13060917
Keywords
oral drug delivery; in situ drug amorphization; polymers; amorphous solid dispersion; laser radiation; plasmonic nanoparticles; pharmaceutical nanotechnology
Categories
Funding
- NordForsk (Nordic University Hub project) [85352]
- Independent Research Fund Denmark [DFF-7026-00052B]
- European Research Council (ERC) under the European Union [758705]
- Swedish Foundation for Strategic Research [FFL18-0043]
- Swedish Research Council [2016-03471]
- Science for Life Laboratory
- Swedish Research Council [2016-03471] Funding Source: Swedish Research Council
- Swedish Foundation for Strategic Research (SSF) [FFL18-0043] Funding Source: Swedish Foundation for Strategic Research (SSF)
- European Research Council (ERC) [758705] Funding Source: European Research Council (ERC)
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The study investigated laser-induced in situ amorphization of the model drug celecoxib with six different polymers. It was found that in situ drug amorphization is possible for drug-polymer combinations where the drug is soluble in the polymer and temperatures during the process are above a certain threshold temperature.
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 (T-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 T-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., T-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 T-DStart.
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