Stability and transdermal absorption of topical amphotericin B liposome formulations.
The aim os this study was to characterize the stability and transdermal absorption of amphotericin B (AMB: 0.05 mg/mg lipid) in hydrogenated soya phosphatidylcholine/cholesterol/charged lipid [dicetyl phosphate (-) or stearylamine (+)] liposomes at molar ratios of 1:1:0, 7:2:0, 7:2:1(-) and 7:2:1(+). The AmB contents in liposomes were determined by HPLC with UV detection at 382 nm. Stabilities of AmB in liposome formulations were compared with those in solution and powder forms, during storage at 4, 30 and 45 degrees C for 90 days. Absorption studies of AmB across the rat skin were conducted, using vertical Franz diffusion cells at 37 degrees C for 24 h. The slowest degradation was observed in the positive liposome (7:2:1(+)AmB), with shelf life of approximately 1 year (30 degrees C). In comparison, the shelf lives of AmB in solution and powder were 4 and 14 days, respectively. AmB in positive liposomes seemed to demonstrate the highest flux in stratum corneum (58 ng/cm(2)/h), while the highest flux in viable epidermis (23 ng/cm(2)/h) was observed in negative liposomes. AmB entrapped in charged liposomes showed sustained skin absorption. The positively charged liposome might be the best formulation for AmB, due to its higher stability than other formulations.
Manosroi
A
A
Pharmaceutical-Cosmetics Raw Materials and Natural Products Research and Development Center, Faculty of Pharmacy, Institute for Science and Technology Research and Development, Chiang Mai University, Chiang Mai 50200, Thailand. pmpti005@chiangmai.ac.th
Kongkaneramit
L
L
Manosroi
J
J
D000279:Administration, Cutaneous; D000666:Amphotericin B / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D008081:Liposomes; D008297:Male; D008855:Microscopy, Electron, Scanning; D019999:Pharmaceutical Solutions; D011208:Powders; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000187:drug effects*; D013997:Time Factors
D000935:Antifungal Agents; D008081:Liposomes; D019999:Pharmaceutical Solutions; D011208:Powders; D000666:Amphotericin B