Inducing effect of liposomalization on the transdermal delivery of hydrocortisone: creation of a drug supersaturated state.
In order to investigate the effect of liposomal drugs on skin delivery, it was postulated that the process of liposomalization might lead the drug to an overpredicted solubility state which has far-reaching implications for drug skin permeation and accumulation. In this regard, conventional (CL) and flexible liposomes (FL) were prepared by the lipid film hydration method and the particles were downsized by sonication using hydrocortisone (HC) as a poorly water soluble model drug. The solutions derived from the whole CL and FL suspensions eluted on a Sephadex G-50 column (SG-50) demonstrated that most part of HC not only resides solely in the water phase but also it might exist in an improved solubility state. The results of the in vitro study using rat abdominal skin and occlusive application indicated that HC penetrated and accumulated much better solely than when associated with CL or FL. In regard to the penetration of the non-entrapped HC associated to liposomes bilayer fragments, a very small amount of phospholipids in the non-liposomal part eluted on SG-50 was found that could not justify by itself the penetration of HC associated to liposome bilayer fragments. It was proposed that all the steps of the liposomes preparation process might contribute for the increased HC solubility state, but definitively the presence of phospholipids played a crucial role on improving the HC solubility in the absence of sodium cholate. In comparison with commercially available ointments, the non-entrapped HC solution derived from the whole CL suspension eluted on SG-50 showed a higher concentration of HC accumulated and more uniformly distributed as well in the epidermis and dermis compartments. In addition, the thermodynamic activity of the non-entrapped HC solutions maintaining a driving force of the drug across the skin barrier pointed out that the level of HC solubility achieved during liposome preparation has far-reaching implication for drug skin permeation and accumulation in the experimental conditions used. The findings also indicated that the non-entrapped drug solutions obtained on the process of liposomalization could be useful on transdermal drug delivery systems, particularly for improving the permeation and accumulation capacity of poorly soluble drugs.
Barichello
José Mario
JM
Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1 Sho-machi, Tokushima 770-8505, Japan.
Handa
Hiroshi
H
Kisyuku
Masatoshi
M
Shibata
Taiki
T
Ishida
Tatsuhiro
T
Kiwada
Hiroshi
H
D000279:Administration, Cutaneous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008081:Liposomes; D008297:Male; D008855:Microscopy, Electron, Scanning; D009824:Ointments; D010316:Particle Size; D010743:Phospholipids / Q000032:analysis / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000737:chemistry; D012869:Skin Absorption / Q000187:drug effects; D013535:Suspensions
D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D008081:Liposomes; D009824:Ointments; D010743:Phospholipids; D013535:Suspensions; D006854:Hydrocortisone