Extended release of a large amount of highly water-soluble diltiazem hydrochloride by utilizing counter polymer in polyethylene oxides (PEO)/polyethylene glycol (PEG) matrix tablets

Abstract

The purpose of this study was to evaluate the feasibility of using a counter polymer in polyethylene oxide (PEO)/polyethylene glycol (PEG) polymeric matrices for the sustained release of a large amount of highly water-soluble drug. PEO/PEG matrix tablets (CR-A) containing four drugs with different water solubilities were prepared to investigate the effect of drug solubility on the drug-release and diffusion properties of PEO/PEG matrices. Cross-linked carboxyvinyl polymer (CVP)/PEO/PEG matrix tablets (CR-B) containing a water-soluble drug, diltiazem hydrochloride (DTZ), were also prepared, and their in vitro characteristics were compared with those of CR-A. Their in vitro drug release properties were evaluated using a dissolution test, and the polymeric erosion and drug diffusion properties of the matrices were also calculated. Drugs with higher solubility in water were released faster for the CR-A. The drug-release rate also increased with the amount of drug loaded. CR-A containing 50% DTZ (by weight) extended drug release by only 6 h. This confirms the difficulty experienced when trying to formulate PEO/PEG matrices for the sustained release of a large amount of highly water-soluble drugs due to large drug diffusion. In an attempt to control this issue, a polymer bearing a charge opposite that of the drug was used to effectively decrease the diffusion of DTZ, resulting in sustained release for 24 h or longer. These results suggested that including counter polymer in the PEO/PEG matrix tablet is a useful tool for achieving the sustained release of a large amount of highly water-soluble drug.