Evaluation of a pharmaceutical preparation of 2-[4-(p-fluorobenzoyl)-piperidin-1-yl]-2'-acetonaphthone hydrochloride with enhanced dissolution rate.
A granule of 2-[4-(p-fluorobenzoyl)-piperidin-1-yl]-2'-acetonaphthone hydrochloride (E2001) with an enhanced dissolution rate (preparation A) prepared by a method previously reported (T. Tokumura, T. Tanaka, Yakuzaigaku, accepted) was evaluated by the dissolution test and its bioavailability in beagle dogs was determined. The dissolution rate of E2001 from preparation A at pH 6.0-6.8 was increased significantly in comparison with that from preparation B (a physical mixture of the same formula). There was no significant difference in Cmax, area under the concentration-time curve (AUC0-6 h), or Tmax between preparations A and B when a dose equivalent to 20 mg of E2001 was administered to the beagle dogs. However, a significant difference was observed between the AUC0-6 h values after oral administration of the two preparations with NaHCO3. These findings suggest that the bioavailability of E2001 from the oral administration preparation A will be higher than that of preparation B.
Tokumura
T
T
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Tanaka
T
T
D000818:Animals; D001682:Biological Availability; D002021:Buffers; D002214:Capsules; D002317:Cardiovascular Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D005069:Evaluation Studies as Topic; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008297:Male; D009281:Naphthalenes / Q000737:chemistry / Q000493:pharmacokinetics*; D010880:Piperidines / Q000737:chemistry / Q000493:pharmacokinetics*; D011208:Powders; D012995:Solubility
D002021:Buffers; D002214:Capsules; D002317:Cardiovascular Agents; D009281:Naphthalenes; D010880:Piperidines; D011208:Powders; C060312:2-(4-(4-fluorobenzoyl)piperidin-1-yl)-2'-acetonaphthone