An Investigation into the Stabilization of Diltiazem HCl Release from Matrices Made from Aged Polyox Powders

Abstract

Abstract. Matrices containing PEO fail to provide stable drug release profiles when stored at elevated temperatures for a period of time. The present study aims to stabilize diltiazem HCl release from matrices made from various molecular weights of polyox powders. To this end, various molecular weights of polyox with and without vitamin E (0.25, 0.5 and 1% w/w) were stored at 40°C for 0, 2, 4 and 8 weeks. The aged polyox powders were then mixed with the model drug at a ratio of 1:1 and compressed into tablets. At different time intervals, the aged polyox with vitamin E were taken out of oven and mixed with the drug (1:1 ratio) and compressed into tablets. Dissolution studies showed a significant increase in diltiazem HCl release rate to occur with increased storage time at 40°C±1 from tablets made from the aged polyox (no vitamin E). This was as a result of depolymerization of the aged polyox powders as compared to the fresh polyox samples. This was confirmed by differential scanning calorimetry (DSC) which showed a reduction in the melting point of the aged samples. Concentrations of vitamin E as low as 0.25% w/w was able to overcome the quick release of drug from the matrices made from aged polyox powders. DSC traces showed that the melting point of aged polyox samples containing vitamin E remained the same as that of the fresh samples. The presence of vitamin E is essential to stabilize the drug release from polyox matrices containing diltiazem HCl.

Evaluations of the Effect of Sodium Metabisulphite on the Stability and Dissolution Rates of Various Model Drugs from the Extended Release Polyethylene Oxide Matrices

“…The results of the current study also illustrated that using SMB in the semi-and poorly water-soluble drugs, such as theophylline and zonisamide, had completely different effect in the beginning of drug release in terms of stability in comparison with the fresh samples without this antioxidant, although drug release decreased as storage time increased. These results particularly are not correlated with the previous data published by Shojaee et al [32,36], who studied the role of sodium metabisulphite on the release rate of diltiazem hydrochloride from polyethylene oxide. This was also a disagreement with earlier data observed in the beginning of this study with propranolol HCl and the reason is given earlier.…”

“…Moreover, results clearly demonstrated that sodium metabisulphite is a good candidate to prevent degradation in different molecular weight PEO in highly soluble drugs such as propranolol HCl (60 mg/ml). The observed results may be deemed expected, according to previous reports by Shojaee et al [32], and our data for both PEO 750 and 303 containing propranolol HCl showed faster release for aged tablets without sodium metabisulphite; on the other hand, drug release was controlled in the presence of this antioxidant. It is interesting to note that there is no any other previous research that studied the effect of SMB in sustained release matrices.…”

“…This could be depending on the effect of sodium metabisulphite which dilated penetration of oxygen into the tablet matrices resulting to no degradation, and a loss in molecular weight of PEO did not occur in PEO. These results complement the previous study carried out by Shojaee et al [32] who investigated the effect of different concentrations SMB on release rate of diltiazem HCl tablet matrices. The results showed that the drug release was controlled and much slower in the presence of this antioxidant On the basis of above information, some of the features in the dissolution rates of PEO can be elaborated particularly by similarity factor (f 2 ) values.…”

Drug release from matrix tablets: physiological parameters and the effect of food

“…Other factors which may also affect the rate at which a drug is released from its hydrophilic gel matrix may include the formulation composition [105-108], the physiochemical properties of the drug and polymer [109][110][111][112][113][114] and the processing and compaction conditions [115][116][117]. All these factors can influence the choice of the polymer viscosity and chemistry used.…”

Evaluation of sesamum gum as an excipient in matrix tablets

“…Hydrophilic matrices are commonly used as oral drug delivery systems and are being increasingly investigated for controlled-release applications because they combine the advantages of not only being easy to formulate but are also economical to produce (Heller et al, 1983;Nokhodchi et al, 2012;Shojaee et al, 2013). The formation of a hydrated viscous layer around the tablet provides a barrier to drug release by opposing penetration of water into the tablet and also movement of dissolved solutes out of the tablet matrix (Bamba et al, 1979;Ghori et al, 2014;.…”