Trials of clear aceclofenac-loaded soft capsules with accelerated oral absorption in human subjects.
To develop an effective oral drug delivery system with accelerated absorption in human subjects for a poorly water-soluble acelofenac, five aceclofenac-loaded soft capsule preparations containing various ratios of different solubilizers were prepared and their dissolution tests were carried out. Among five preparations tested, a preparation with ethanolamine was selected as a formula of aceclofenac soft capsule (Korea United Pharm. Co. Ltd., Clanza S, since it was clear in appearance and showed the fastest dissolution rate due to the solubility-enhancing effect of aceclofenac. To evaluate and compare the pharmacokinetics of acelofenac-loaded soft capsules with the conventional aceclofenac tablets (Dae-Woong Pharm. Co. Ltd., Airtal) in human subjects; 14 normal healthy male volunteers (age 20-25 years old) were divided into two groups and a randomized 2 x 2 cross-over study was performed. Following oral administration of one tablet or capsule, each containing 100mg of aceclofenac, blood samples were collected at the predetermined time intervals and the concentration of aceclofenac in plasma was determined by HPLC method using UV detector. The AUC, Cmax, MRT, t1/2 and Kel of aceclofenac delivered from soft capsule were not significantly different from those from aceclofenac-loaded conventional tablet. However, soft capsule gave significantly higher initial concentration and significantly faster Tmax of aceclofenac than did conventional tablet, suggesting that the soft capsule with ethanolamine showed the faster absorption of aceclofenac in human subjects. Thus, the clear aceclofenac-loaded soft capsule with ethanolamine was a more effective oral dosage form with fast absorption for poorly water-soluble aceclofenac.
Yong
Chul Soon
CS
College of Pharmacy, Yeungnam University, 214-1 Dae-Dong, Gyongsan 712-749, South Korea.
Oh
Yu-Kyoung
YK
Lee
Kyung Hee
KH
Park
Sang-Man
SM
Park
Young-Joon
YJ
Gil
Young Sig
YS
Yu
Chang Hun
CH
Yoo
Bong-Kyu
BK
Woo
Jong Soo
JS
Kim
Jong Oh
JO
Rhee
Jong-Dal
JD
Kim
Chong-Kook
CK
Choi
Han-Gon
HG
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004008:Diclofenac / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D019856:Ethanolamine / Q000737:chemistry; D006207:Half-Life; D006801:Humans; D008297:Male; D008536:Meglumine / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D004008:Diclofenac; D011092:Polyethylene Glycols; D019856:Ethanolamine; D008536:Meglumine; C056498:aceclofenac