Formulation and in vitro evaluation of transdermal patches of melatonin.
The present study was undertaken to prepare and evaluate monolithic drug-inadhesive type transdermal patches of melatonin containing penetration enhancers such as fatty alcohols, fatty acids, and terpenes. The patches were prepared using Eudragit E 100 as the adhesive polymer. The release profile of melatonin from control as well as enhancer-containing patches showed an initial burst of melatonin release for up to 4 hours and then a plateau after 8 hours. The release profiles of melatonin from patches containing various enhancers were similar to the control patch. However, the addition of enhancers in the patch increased the permeation of melatonin through hairless rat skin. The flux values of patches containing octanol, nonanoic acid, and myristic acid were higher than the control patch (no enhancer), but the differences were not statistically significant (P>0.05). Decanol, myristyl alcohol, and undecanoic acid at 5% concentrations showed significantly higher flux values through hairless rat skin (enhancement ratios 1.7, 1.5, and 1.6 for decanol, myristyl alcohol, and undecanoic acid, respectively) (P<0.05). Menthol and limonene at 5% w/w showed maximum permeation of melatonin among all enhancers studied (enhancement ratios=2.1 and 2.0 for menthol and limonene, respectively) (P<0.001). In general, there was about 4-6 hours of lag time observed before a steady state flux of melatonin was achieved. Though the flux of melatonin observed in the present study is 5-10 times higher than the required delivery rate in humans, it must be noted that the present study was performed using hairless rat skin, which is generally more permeable compared to human skin. Further studies using human skin would prove the usefulness of these patches.
Kanikkannan
N
N
Division of Pharmaceutics, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida 32307, USA.
Andega
S
S
Burton
S
S
Babu
R J
RJ
Singh
Mandip
M
D000179:Acrylates / Q000737:chemistry; D000277:Adjuvants, Pharmaceutic / Q000737:chemistry; D000279:Administration, Cutaneous; D000818:Animals; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D005227:Fatty Acids / Q000737:chemistry; D005233:Fatty Alcohols / Q000737:chemistry; D066298:In Vitro Techniques; D008297:Male; D008550:Melatonin / Q000008:administration & dosage* / Q000737:chemistry*; D010539:Permeability; D011108:Polymers / Q000737:chemistry; D051381:Rats; D012869:Skin Absorption; D012995:Solubility; D013729:Terpenes / Q000737:chemistry
D000179:Acrylates; D000277:Adjuvants, Pharmaceutic; C477020:Eudragit E100; D005227:Fatty Acids; D005233:Fatty Alcohols; D011108:Polymers; D013729:Terpenes; D008550:Melatonin