TY - JOUR
T1 - Development of novel fast-dissolving tacrolimus solid dispersion-loaded prolonged release tablet
AU - Cho, Jung Hyun
AU - Kim, Yong Il
AU - Kim, Dong Wuk
AU - Yousaf, Abid Mehmood
AU - Kim, Jong Oh
AU - Woo, Jong Soo
AU - Yong, Chul Soon
AU - Choi, Han Gon
PY - 2014/4/11
Y1 - 2014/4/11
N2 - The goal of this research was to develop a novel prolonged release tablet bioequivalent to the commercial sustained release capsule. A number of tacrolimus-loaded fast-dissolving solid dispersions containing various amounts of DOSS were prepared using the spray drying technique. Their solubility, dissolution and pharmacokinetics in rats were studied. DOSS increased drug solubility and dissolution in the solid dispersions. Compared with the drug powder, the solubility, dissolution and bioavailability of tacrolimus with the fast-dissolving solid dispersion containing tacrolimus/HP-β-CD/DOSS in the weight ratio of 5:40:4 were boosted by approximately 700-, 30- and 2-fold, respectively. Several tablet formulations were accomplished with this solid dispersion in combination with various ratios of HPMC/ethylcellulose. The release behaviour and pharmacokinetic studies in beagle dogs were assessed compared with the commercial prolonged release capsule. A decrease in HPMC/ethylcellulose ratios reduced the dissolution of tacrolimus from the tablets. Particularly, the tacrolimus-loaded prolonged release tablet consisting of fast-dissolving tacrolimus solid dispersion, HPMC, ethylcellulose and talc at the weight ratio of 20:66:112:2 exhibited a dissolution profile similar to that produced by the commercial prolonged release capsule. Furthermore, there were no significant differences in the AUC, Cmax, Tmax and MRT values between them in beagle dogs. Consequently, this tacrolimus-loaded prolonged release tablet might be bioequivalent to the tacrolimus-loaded commercial capsule.
AB - The goal of this research was to develop a novel prolonged release tablet bioequivalent to the commercial sustained release capsule. A number of tacrolimus-loaded fast-dissolving solid dispersions containing various amounts of DOSS were prepared using the spray drying technique. Their solubility, dissolution and pharmacokinetics in rats were studied. DOSS increased drug solubility and dissolution in the solid dispersions. Compared with the drug powder, the solubility, dissolution and bioavailability of tacrolimus with the fast-dissolving solid dispersion containing tacrolimus/HP-β-CD/DOSS in the weight ratio of 5:40:4 were boosted by approximately 700-, 30- and 2-fold, respectively. Several tablet formulations were accomplished with this solid dispersion in combination with various ratios of HPMC/ethylcellulose. The release behaviour and pharmacokinetic studies in beagle dogs were assessed compared with the commercial prolonged release capsule. A decrease in HPMC/ethylcellulose ratios reduced the dissolution of tacrolimus from the tablets. Particularly, the tacrolimus-loaded prolonged release tablet consisting of fast-dissolving tacrolimus solid dispersion, HPMC, ethylcellulose and talc at the weight ratio of 20:66:112:2 exhibited a dissolution profile similar to that produced by the commercial prolonged release capsule. Furthermore, there were no significant differences in the AUC, Cmax, Tmax and MRT values between them in beagle dogs. Consequently, this tacrolimus-loaded prolonged release tablet might be bioequivalent to the tacrolimus-loaded commercial capsule.
KW - Bioequivalence in beagle dogs
KW - Ethylcellulose
KW - Fast-dissolving solid dispersion
KW - Hydroxypropyl methylcellulose
KW - Prolonged release tablet
KW - Tacrolimus
UR - http://www.scopus.com/inward/record.url?scp=84892687255&partnerID=8YFLogxK
U2 - 10.1016/j.ejps.2013.12.016
DO - 10.1016/j.ejps.2013.12.016
M3 - Article
C2 - 24388864
AN - SCOPUS:84892687255
SN - 0928-0987
VL - 54
SP - 1
EP - 7
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
IS - 1
ER -