The effects of electrically assisted methods on transdermal delivery of nalbuphine benzoate and sebacoyl dinalbuphine ester from solutions and hydrogels.
The aim of this study was to assess the effects of iontophoresis and electroporation on transdermal delivery of nalbuphine (NA) and its two novel prodrugs: nalbuphine benzoate (NAB) and sebacoyl dinalbuphine ester (SDN) from solutions as well as from hydrogels. Hydroxypropyl cellulose (HPC) and carboxymethyl cellulose (CMC) were used in hydrogel formulations to evaluate their feasibility for delivery of NA and its prodrugs. Application of iontophoresis or electroporation significantly enhanced the in vitro permeation of NA and its prodrugs. The enhancement effect was more pronounced after applying iontophoresis. The combination of two electrically assisted methods enhanced the delivery of NA; however, no such enhancement was observed for the permeation of NAB and SDN. Hydrogels containing low concentration HPC did not affect the passive as well as electrically assisted permeation of NA and its prodrugs. The increase of hydrogel concentration as well as molecular weight significantly decreased the electrically assisted permeation of NA, whereas the permeation of NAB and SDN remained unchanged. For the electrically assisted permeation from CMC-based hydrogels, the reduced permeation from higher percentage of CMC hydrogels may be attributed the viscosity effect as well as the ion competition effect. The above results demonstrated that lipophilicity and molecular size, as well as hydrogel compositions had significant effects on skin permeation of NA, NAB and SDN via passive diffusion or under the electric field.
Huang
Jeng-Fen
JF
Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan Hsien, Taiwan.
Sung
K C
KC
Hu
Oliver Yoa-Pu
OY
Wang
Jhi-Joung
JJ
Lin
Yi-Hsin
YH
Fang
Jia-You
JY
D000279:Administration, Cutaneous; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D002266:Carboxymethylcellulose Sodium; D002482:Cellulose / Q000031:analogs & derivatives; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D004558:Electric Stimulation; D018274:Electroporation; D005079:Excipients; D005260:Female; D020100:Hydrogels; D066298:In Vitro Techniques; D007478:Iontophoresis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009266:Nalbuphine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019999:Pharmaceutical Solutions; D011355:Prodrugs; D014783:Viscosity
D000701:Analgesics, Opioid; D005079:Excipients; D020100:Hydrogels; D019999:Pharmaceutical Solutions; D011355:Prodrugs; C420448:sebacoyl dinalbuphine ester; D002482:Cellulose; C008079:hydroxypropylcellulose; D002266:Carboxymethylcellulose Sodium; D009266:Nalbuphine