The influence of vitamin E succinate on the stability of polyethylene oxide PEO controlled release matrix tablets.

Abstract

Hydrophilic matrices are a principal technology used for extended release (ER) oral dosage forms and a recent review concluded that their development is currently one of the most important challenges in pharmaceutical research. High molecular weight polyethylene oxides (PEOs) have been proposed as an alternative to hydroxypropylmethylcellulose (HPMC) for the manufacture of controlled release matrix tablets. It is known that PEO's are prone to oxidative degradation which can occur by chain scission and can be catalyzed by metal ions. In this study, we investigated the stability of PEO matrix tablets, of different molecular weight, containing diltiazem hydrochloride, when stored at 40 °C. The results show that there were dramatic increases in the release rate of the diltiazem following storage over only a few weeks, resulting in immediate release profiles after eight weeks, even for the highest molecular weight grade. We employed Gel permeation chromatography (GPC), viscosity and differential scanning calorimetry (DSC) techniques to try and determine the underlying causes of these dramatic shifts in dissolution profiles on storage. The results showed that there were significant decreases in the molecular weight of the PEO's during storage. The second part of the study looked at the addition of three different levels of vitamin E succinate to the tablets. The results clearly demonstrate the ability of the added antioxidant to reverse the significant reductions in molecular weight seen using GPC, viscosity and DSC. Importantly the addition of the antioxidant was able to stabilize the release profile of the diltiazem especially when present at a 1% level. Researchers and those working in pharmaceutical development should be aware of the potential stability risks when making matrix tablets containing PEO's and may wish to consider the addition of an antioxidant to the tablet formulation.