Effects of fatty acids and iontophoresis on the delivery of midodrine hydrochloride and the structure of human skin.
OBJECTIVE
The purpose of this work was to investigate if fatty acids can increase the iontophoretic delivery of midodrine hydrochloride through human dermatomed skin and to observe the effects of iontophoresis and fatty acids on skin using SEM.


METHODS
After prehydration for 1 h, human dermatomed skin was treated with 0-0.3 M fatty acids (oleic acid, linoleic acid, decanoic acid, and lauric acid) in propylene glycol (PG) for 1 h. Then the fatty acid solution was replaced by 1% midodrine hydrochloride aqueous solution, and 0.1 mA/cm2 constant current was applied. Samples were taken over 24 h and analyzed by HPLC. After the treatments outlined above, the epidermis was separated, fixed with glutaraldehyde, and dehydrated for SEM.


RESULTS
SEM studies revealed that only 1 h of treatment with fatty acids opened up the tightly compact stratum corneum cell layer, and the permeation study showed a significant increase of the permeability of skin to midodrine hydrochloride after fatty acid treatment.


CONCLUSIONS
Using 5% oleic acid pretreatment, with the electrical current offset at 0.1 mA/cm2, the daily delivery of midodrine hydrochloride can provide an adequate clinical application. The enhancement of passive and iontophoretic delivery by fatty acids may be occurring through the same mechanism.
Wang
Yiping
Y
Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
Fan
Qiuxi
Q
Song
Yifan
Y
Michniak
Bozena
B
D000277:Adjuvants, Pharmaceutic / Q000737:chemistry / Q000494:pharmacology; D000279:Administration, Cutaneous; D000959:Antihypertensive Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D003652:Decanoic Acids / Q000737:chemistry / Q000494:pharmacology; D004817:Epidermis / Q000033:anatomy & histology / Q000378:metabolism*; D005079:Excipients / Q000737:chemistry; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007478:Iontophoresis; D007850:Lauric Acids / Q000737:chemistry / Q000494:pharmacology; D019787:Linoleic Acid / Q000737:chemistry / Q000494:pharmacology; D008879:Midodrine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019301:Oleic Acid / Q000737:chemistry / Q000494:pharmacology; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019946:Propylene Glycol / Q000737:chemistry; D012869:Skin Absorption / Q000187:drug effects; D012879:Skin Physiological Phenomena
D000277:Adjuvants, Pharmaceutic; D000959:Antihypertensive Agents; D003652:Decanoic Acids; D005079:Excipients; D005227:Fatty Acids; D007850:Lauric Acids; D011355:Prodrugs; C030358:lauric acid; D019301:Oleic Acid; C031071:decanoic acid; D019946:Propylene Glycol; D008879:Midodrine; D019787:Linoleic Acid