Title : PEO Hydrophilic tablet matrix systems as controlled release oral dosage forms using different water soluble drugs and antioxidants
Abstract:
Hydrophilic matrix systems are currently some of the most widely used drug delivery systems for controlled release oral dosage forms. Among a variety of polymers, polyethylene oxide (PEO) is one of the most important materials used in pharmaceutical formulations. As PEO is sensitive to thermal oxidation, it is susceptible to free radical oxidative attack. The properties of PEO are subject to changes as a result of degradation, ultimately to the point where the material is no longer able to fulfill its expected function. The mode, extent and mechanism of degradation are strongly dependent on the intensity and duration of the physical and chemical stresses and drug solubility, to which the polymer is exposed. An investigation of it’s stability was carried out by making several batches of four model drugs namely, Diltiazem, Propranolol, Theophylline and Zonisamide matrix tablets at ratios of 1:1 and 2:1( both ratios only for Diltiazem), using different fillers namely lactose, dicalcium phosphate (DCP), and mannitol with various molecular weight (MW) grades of PEO (750, 1105, 301, 303). In addition, antioxidants were also incorporated into the formulation which included vitamin E and sodium metabisulfite. The results of the present study suggests that depending on the substituent, different interactions between the drug and PEO can be created and can alter the erosion of the polymer and in turn the release of the drug. The findings suggest that storage conditions of the matrix tablets, solubility of drugs and the molecular weight of polymer influence drug release from the matrix. Generally, increased drug release rates were prevalent in soluble drug formulations (Diltiazem, Propranolol) when they were stored at an elevated temperature (40°C), but were not observed in zonisamide (poorly soluble) matrices and polymer formulations containing higher molecular weight PEO 303, with medium soluble drug theophylline. The results also showed that drug release at a ratio 2:1was faster than 1:1 and tablets stored for a longer storage time had a faster drug release than freshly made samples (8 > 4 > 2 > 0 weeks). This was due to polymers being subjected to oxidative degradation confirmed by showing a reduction in the melting point of the aged polymer formulations due to depolymerisation. The results also showed that vitamin E succinate and sodium metabisulphite were successful in stabilizing soluble drug diltiazem and propranolol formulations. For partially soluble and poorly soluble drug formulations, stability depended on the types of antioxidant and the molecular weight of Polyox. Interestingly, Vitamin E was found to be the most suitable stabilizer for PEO with the polymer being more thermally stable after Vitamin E was added. The addition of diluents, into the formulations showed that DCP produced a reduction in drug release compared to mannitol and lactose. This may be due to the difference in solubility of the diluents which in turn affected the rate and mechanism of drug release from the swellable matrix, although all these fillers had similar effect on release rate of diltiazem as a highly soluble drug. The results proved that the presence of antioxidants and fillers are necessary to stabilize drug release from polyox matrices when stored at elevated temperature. Finally, it is evident from the aged PEO powder study that similar results were obtained from aged tablets and tablets made with aged PEO powder containing diltiazem, when they were stored at 40°C, as well as in presence of vitamin E in terms of stability.
