A new index, the core erosion ratio, of compression-coated timed-release tablets predicts the bioavailability of acetaminophen.
Although compression-coated tablets are a commonly used timed-release drug delivery technology, their utility is often limited by poor bioavailability. To try to improve the bioavailability of these tablets, the effect of their core composition of compression-coated tablet on in vivo pharmacokinetics was investigated. First, the extent of mass reduction of cores in different compression-coated tablet core formulations was used to establish a new index, the core erosion ratio. The data show that adding excipients with high water solubility to the core results in a greater core erosion ratio. Next, to elucidate the effect of core erosion ratio on in vivo acetaminophen (AAP) release, three compression-coated tablet formulations with similar in vitro AAP release profiles but different core erosion ratios were administered to four fasted dogs. The time for first appearance (TFA) of AAP in plasma did not differ significantly among formulations, indicating that the in vivo lag time was the same for all formulations. In separate experiments, necroscopy revealed that 3h after oral administration, the tablets were located in the ileum and colon and that all three formulations had identical GI transit times. However, the area under the AAP plasma concentration-time curve was greater in dogs given formulations with larger core erosion ratios. These results suggest that a formulation with a large core erosion ratio can significantly increase in vivo drug release from compression-coated tablets, leading to increased drug absorption from the lower GI tract.
Sawada
T
T
DDS Research, Novel Pharmaceutical Research Laboratories, Institute for Technology Development, Yamanouchi Pharmaceutical Co., Ltd., 180 Ozumi, Yaizu-shi, Shizuoka 425-0072, Japan. sawada_t@yamanouchi.co.jp
Sako
K
K
Fukui
M
M
Yokohama
S
S
Hayashi
M
M
D000082:Acetaminophen / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D019245:Compressive Strength; D004285:Dogs; D005079:Excipients; D005544:Forecasting; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D012995:Solubility; D013608:Tablets, Enteric-Coated; D013997:Time Factors
D005079:Excipients; D013608:Tablets, Enteric-Coated; D000082:Acetaminophen