title: 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 6h. 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 24h 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.
authors.affiliation: Pharmaceutical Research and Technology Labs., Astellas Pharma Inc., Shizuoka, Japan. hiroyuki.kojima@jp.astellas.com
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kojima
authors.forename: Keiichi
authors.initials: K
authors.lastname: Yoshihara
authors.forename: Toyohiro
authors.initials: T
authors.lastname: Sawada
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kondo
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sako
mesh_terms: D003692:Delayed-Action Preparations; D004110:Diltiazem / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013607:Tablets
chemical_list: D003692:Delayed-Action Preparations; D011108:Polymers; D013607:Tablets; D011092:Polyethylene Glycols; D004110:Diltiazem