Formulation and evaluation of ubidecarenone transdermal delivery systems.
OBJECTIVE
This study is aimed to examine the feasibility of developing ubidecarenone (coenzyme Q(10), CoQ(10)) transdermal delivery systems (TDS).


METHODS
In vitro permeation study using solution formulation and pressure-sensitive adhesive (PSA) TDS and in vivo pharmacokinetic study were conducted.


RESULTS
When using solution formulations, isopropyl alcohol (103.39 +/- 1.61), ethyl alcohol (81.55 +/- 7.27), and the mixture of diethylene glycol monoethyl ether (DGME)/propylene glycol monolaurate (PGML) at the ratio of 60:40 (91.08 +/- 26.07) showed high flux (microg/cm(2)/hour). The addition of fatty acids to DGME-PGML failed to show profound enhancing effects; only unsaturated fatty acids such as linoleic acid and oleic acid at 3% and caprylic acid at 3% and 10% slightly increased permeation flux. CoQ(10) from the acrylic PSA TDS showed biphasic permeation profile that was permeated very rapidly up to the first 12 hours, and after that, permeation rate became slower. Overall, 6% fatty acids showed high permeation rates and the highest maximum flux of 9.3 microg/cm(2)/hour was obtained with a formulation containing 6% lauric acid in DGME-PGML (60:40). The in vivo pharmacokinetic study using TDS with 6% fatty acids in DGME-PGML (60:40) showed that the absorption of CoQ(10) decreased in the following order: TDS containing linoleic acid > oral dosage form > TDS with oleic acid > TDS with lauric acid > TDS with caprylic acid > TDS with capric acid. TDS containing oleic acid showed preferable pharmacokinetic profile with respect to lower C(max), comparable AUC, and prolonged t(1/2) and T(max) compared to oral administration of drug.


CONCLUSIONS
For effective transdermal delivery system of CoQ(10), 6% linoleic acid or oleic acid in DGME-PGML (60:40) could be employed.
Jung
Sun Young
SY
College of Pharmacy, Ewha Womans University, Seoul, Korea.
Kang
Eun Young
EY
Choi
Yoon Jung
YJ
Chun
In Koo
IK
Lee
Byung Koo
BK
Gwak
Hye Sun
HS
D000279:Administration, Cutaneous; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D005079:Excipients; D005227:Fatty Acids / Q000737:chemistry; D006207:Half-Life; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption / Q000502:physiology; D012995:Solubility; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics
D000975:Antioxidants; D005079:Excipients; D005227:Fatty Acids; D014451:Ubiquinone; C024989:coenzyme Q10