Evaluations of the effect of sodium metabisulfite on the stability and dissolution rates of various model drugs from the extended release polyethylene oxide matrices

Purpose: This study examines the effect of sodium metabisulfite (SMB) as an antioxidant on the stability and release of various model drugs namely propranolol HCl, theophylline and zonisamide from the polyethylene oxide (PEO) tablets. The antioxidant was used to minimise degradation and instability of the manufactured tablets when stored at 40°C (55±5 % RH) over 8 weeks. Method: Multiple batches of tablets weighing 240 mg (50% w/w) with a ratio of 1:1 drug: polymer and 1% (w/w) sodium metabisulfite containing different model drugs and various molecular weights of PEO 750 and 303 were produced. Results: The results indicated that the use of sodium metabisulfite marginally assisted in reducing drug release and degradation via oxidation in propranolol HCl tablets containing both PEO 750 and 303. In the case of poorly and semi-soluble drugs (zonisamide and theophylline) the formulations with both PEO showed entirely superimposable phenomenon and different release profiles compared to control samples (matrices without SMB). DSC study demonstrated the modifications of the polymer due to degradation and observed the effect of SMB on the thermal degradation of the PEO matrices. Conclusion: The use of antioxidant has assisted in retaining the stability of the manufactured tablets with different model drugs especially those with the highly soluble drug that are susceptible to rapid degradation. This has been reflected by an extended release profile of various drugs used at various stages of the storage time up to 8 weeks

Characterisation of water behaviour in cellulose ether polymers using low frequency dielectric spectroscopy

The behaviour of water in hydroxypropylmethylcellulose (HPMC) K100LV, K4M, K15M, K100M, E4M, F4M and HPC polymers was characterised using low frequency dielectric spectroscopy (LFDS). Dielectric responses of 25% (w/w) HPMC K15M gels and deionised water were found to be similar at +22 and 0 °C. However, at -30 °C, a dielectric response typical of a solid was apparent. The melting of frozen water within gels was detected as increases in the magnitude of the dielectric response with increase in temperature. More than one phase transition was visible in the majority of gels studied which may be related to the presence of different states of water melting at different temperatures. In addition to polymer concentration, both polymer molecular weight and substitution level influenced the nature of the transitions. The magnitude of the dielectric response was increased in all HPMC gel systems in comparison to the response seen in deionised water. Drug addition affected the transitions occurring during the melting of ice in the gels. This may be related to the presence of ionic species in the systems. LFDS studies on cellulose ether gels have provided some interesting evidence for the existence of more than one state of water within such gel systems. The results are in good agreement with thermal analysis findings in similar gel systems

Evaluating the Swelling, Erosion and Compaction Properties of Cellulose Ethers

Swelling, erosion, deformation and consolidation properties can affect the performance of cellulose ethers, the most commonly used matrix former in hydrophilic sustained tablet formulations. The present study was designed to comparatively evaluate the swelling, erosion, compression, compaction and relaxation properties of the cellulose ethers in a comprehensive study using standardised conditions. The interrelationship between various compressional models and the inherent deformation and consolidation properties of the polymers on the derived swelling and erosion parameters are consolidated. The impact of swelling (Kw) on erosion rates (KE) and the inter-relationship between Heckel and Kawakita plasticity constants was also investigated. It is evident from the findings that the increases in both substitution and polymer chain length led to higher Kw, but a lower KE; this was also true for all particle size fractions regardless of polymer grade. Smaller particle size and high substitution levels tend to increase the relative density of the matrix but reduce porosity, yield pressure (Py), Kawakita plasticity parameter (b-1) and elastic relaxation. Both KW vs KE (R2 = 0.949-0.980) and Py vs b-1 correlations (R2 = 0.820-0.934) were reasonably linear with regards to increasing hydroxypropyl substitution and molecular size. Hence, it can be concluded that the combined knowledge of swelling and erosion kinetics in tandem with the in and out-of-die compression findings can be used to select a specific polymer grade and further to develop and optimise formulations for oral controlled drug delivery applications