The influence of chirality, physicochemical properties, and permeation enhancers on the transdermal permeation of amlodipine across rat skin.
OBJECTIVE
This study was aimed at investigating the possible relationship between the physical properties and the permeation of S-amlodipine and RS-amlodipine and studying the possible enantioselectivity of permeation of amlodipine in the presence and absence of enhancers, such as terpene enhancers and ethanol.


METHODS
The solubility of S-amlodipine and RS-amlodipine was measured using the shake-flask method. The thermodynamic properties were investigated by differential scanning calorimetry (DSC). The type of racemate amlodipine was investigated by DSC and Fourier transform infrared spectroscopy (FTIR). The permeability of racemate and enantiomers of amlodipine through rat epidermis in vitro was investigated using the modified Franz diffusion cell.


RESULTS
The aqueous solubility of S-amlodipine was higher than that of RS-amlodipine. The melting temperature and enthalpy of fusion of S-amlodipine were lower than those of RS-amlodipine. RS-amlodipine was a racemic compound. The permeation of the enantiomers of amlodipine from RS-amlodipine reservoir showed no significant differences in the presence and absence of enhancers, but the permeation of S-amlodipine from S-amlodipine reservoir was significantly higher than that of RS-amlodipine from RS-amlodipine reservoir 30% ethanol, 50% ethanol, and terpene enhancers could not influence the difference in permeation between S-amlodipine and RS-amlodipine, but 75% ethanol could reduce the difference.


CONCLUSIONS
These results suggested that there was no enantioselectivity of the enantiomers of amlodipine from RS-amlodipine reservoir in the presence and absence of enhancers, but the differences in physical properties between S-amlodipine and RS-amlodipine led to the difference in permeation across rat skins.
Zeng
Aiguo
A
School of Medicine, Xi'an Jiaotong University, Xi'an, PR China.
Wang
Changhe
C
Yuan
Bingxiang
B
Yang
Guangde
G
Fu
Qiang
Q
D000279:Administration, Cutaneous; D017311:Amlodipine / Q000737:chemistry* / Q000493:pharmacokinetics*; D000818:Animals; D055598:Chemical Phenomena / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D010539:Permeability / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology*; D013237:Stereoisomerism
D017311:Amlodipine