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

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.

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Materials: Celecoxib (CCX, Mw = 381.4 g/mol) and magnesium stearate (MgSt, Mw = 591.3 g/mol) were purchased from Fagron Nordic A/S (Copenhagen, Denmark). Kollidon® VA64 (VA64, polyvinylpyrrolidone-vinyl acetate copolymer, Mw = 38,200 g/mol) and Soluplus® (Soluplus, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, Mw = 118,000 g/mol) were kindly supplied by BASF (Ludwigshafen, Germany). Shin-Etsu AQOAT® (HPMCAS, hypromellose acetate succinate, Mw = 18,000 g/mol) was received as a gift from Shin-Etsu Chemical Co., Ltd. (Tokyo, Japan). Eudragit® EPO (EPO, Amino methacrylate copolymer, Mw = 47,000 g/mol) and Eudragit® EL 100 (EL100, anionic methacrylic acid methyl methacrylate copolymer, Mw = 125,000 g/mol) were supplied as a gift from Evonik Nutrition & Care GmbH (Darmstadt, Germany). Parteck® MXP Polyvinyl alcohol (PVA, Mw = 26,300 g/mol) was a gift from Merck KGaA (Darmstadt, Germany).

Silver acetate (99.8% anhydrous) was purchased from Alfa Aesar (Kandel, Germany). Hexamethyldisiloxane (≥98%), acetonitrile (99.8% anhydrous), and 2-ethylhexanoic acid (99%) were purchased from Sigma-Aldrich (Stockholm, Sweden). The oxygen gas for the flame spray pyrolysis synthesis (FSP) was from Strandmøllen (Ljungby, Sweden).
Ethanol (>99.7%, HPLC grade) was purchased from VWR International (Leuven, Belgium). Purified water used for the mobile phase in the HPLC experiments was prepared using a MilliQ water system from LabWater (Los Angeles, CA, USA). Silica gel with indicator (orange gel) as a granulate was purchased from Merck KGaA (Darmstadt, Germany). All chemicals were used as received.

Article information: Hempel, N.-J.; Merkl, P.; Knopp, M.M.; Berthelsen, R.; Teleki, A.; Sotiriou, G.A.; Löbmann, K. The Influence of Drug–Polymer Solubility on Laser-Induced In Situ Drug Amorphization Using Photothermal Plasmonic Nanoparticles. Pharmaceutics 202113, 917.

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