The Effect of the Molecular Weight of Polyvinylpyrrolidone and the Model Drug on Laser-Induced In Situ Amorphization

Laser radiation has been shown to be a promising approach for in situ amorphization, i.e., drug amorphization inside the final dosage form. Upon exposure to laser radiation, elevated temperatures in the compacts are obtained. At temperatures above the glass transition temperature (T_g) of the polymer, the drug dissolves into the mobile polymer. Hence, the dissolution kinetics are dependent on the viscosity of the polymer, indirectly determined by the molecular weight (M_w) of the polymer, the solubility of the drug in the polymer, the particle size of the drug and the molecular size of the drug.

Using compacts containing 30 wt% of the drug celecoxib (CCX), 69.25 wt% of three different M_w of polyvinylpyrrolidone (PVP: PVP12, PVP17 or PVP25), 0.25 wt% plasmonic nanoaggregates (PNs) and 0.5 wt% lubricant, the effect of the polymer M_w on the dissolution kinetics upon exposure to laser radiation was investigated. Furthermore, the effect of the model drug on the dissolution kinetics was investigated using compacts containing 30 wt% of three different drugs (CCX, indomethacin (IND) and naproxen (NAP)), 69.25 wt% PVP12, 0.25 wt% PN and 0.5 wt% lubricant.

In perfect correlation to the Noyes–Whitney equation, this study showed that the use of PVP with the lowest viscosity, i.e., the lowest M_w (here PVP12), led to the fastest rate of amorphization compared to PVP17 and PVP25. Furthermore, NAP showed the fastest rate of amorphization, followed by IND and CCX in PVP12 due to its high solubility and small molecular size.

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Materials: Celecoxib (CCX, M_w = 381.4 g/mol), indomethacin (IND, M_w = 357.8 g/mol), naproxen (NAP, M_w = 230.3 g/mol) and magnesium stearate (M_w = 591.3 g/mol) were purchased from Fagron Nordic A/S (Copenhagen, Denmark). Kollidon^® 12 PF (polyvinylpyrrolidone (PVP), PVP12, M_w ~2500 g/mol), Kollidon^® 17 PF (PVP17, M_w ~9000 g/mol) and Kollidon^® 25 (PVP25, M_w ~24,000 g/mol) were a kind gift from BASF (Ludwigshafen, 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 (flow: 5.0 L/min) for the flame-spray-pyrolysis synthesis was from Strandmøllen (Ljungby, Sweden).