Abstract

Poly(ethylene oxide) (PEO)-based hot melt extrudates offer an interesting potential as oral controlled drug delivery systems and can provide additional advantages, such as reducing the risk of drug abuse. Different polymer molecular weight PEOs are commercially available and can be used to prepare drug-loaded hot melt extrudates. Importantly, the macromolecular chain length impacts crucial system features, including the swelling and erosion kinetics of the systems, which determine the conditions for drug release. The aim of this study was to monitor the effects of changes in the PEO molecular weight (100, 200, 300, 600, 900, 1,000, 2,000, 4,000, 5,000, vs. 7,000 kDa) on theophylline release from hot melt extrudates and to try to better understand the observed tendencies. The drug loading was kept constant at 10 %. Interestingly, theophylline release substantially slowed down when increasing the PEO polymer molecular weight from 100 kDa to 600 kDa, but a further increase to 7,000 kDa led only to a slight additional decrease in the drug release rate. Upon exposure to the release medium, a more or less important gel layer formed (depending on the PEO chain length), consisting of a transparent and a non-transparent part (due to the presence of non-dissolved theophylline crystals). These gel layers surrounded (solid) cores, which decreased in size with time. No clear correlation was found between: (i) the impact of the PEO polymer molecular weight on the drug release kinetics and (ii) the impact of the PEO polymer molecular weight on the dynamic changes in the thicknesses of the transparent and non-transparent gel layers, the dimensions of the (solid) cores, the dry mass (%), remaining PEO (%) or water content (%) of the different system portions. Interestingly, such a correlation was only observed with respect to the changes in the volume of the “(solid) cores + non-transparent gels” (dominated by the changes in their diameters).

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