Complex formation of sericoside with hydrophilic cyclodextrins: improvement of solubility and skin penetration in topical emulsion based formulations.
The main objective of this study was to devise novel methods for improving the solubility of the anti-inflammatory triterpenoid sericoside, the main component of Terminalia sericea extract, thus enabling its incorporation into topical formulations. Sericoside was stabilized by complex formation with hydrophilic derivatives of beta- and gamma-cyclodextrins in a molar ratio of 1.0:1.1. The complex of extract and cyclodextrin was equilibrated in water at 25 degrees C for approximately 24 h. The dehydrated complexes of T. sericea extract and cyclodextrin were characterized by differential scanning calorimetry, thermogravimetry analysis and X-ray diffraction. Complex formation with beta-cyclodextrin as well as gamma-cyclodextrin derivatives was detectable using these three analytical tools; however, only complexes with gamma-cyclodextrin derivatives showed stability upon storage after incorporation into topical o/w or w/o formulations. Furthermore, a T. sericea extract/gamma-cyclodextrin complex incorporated in an o/w formulation resulted in a 2.6-fold higher percutaneous penetration of sericoside in in vitro excised pig skin as compared to pure T. sericea extract. For the first time, the virtually insoluble anti-inflammatory active sericoside was incorporated into a topical emulsion based formulation in a stable manner, resulting in efficient skin penetration.
Rode
T
T
Department of Pharmaceutics and Biopharmaceutics, University of Kiel, Kiel, Germany.
Frauen
M
M
Müller
B W
BW
Düsing
H J
HJ
Schönrock
U
U
Mundt
C
C
Wenck
H
H
D000287:Administration, Topical; D000473:Alkanes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D003505:Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D004355:Drug Stability; D004655:Emulsions; D005960:Glucosides; D066298:In Vitro Techniques; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry* / Q000493:pharmacokinetics*; D010539:Permeability; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D018517:Plant Roots / Q000737:chemistry; D012867:Skin / Q000378:metabolism*; D012995:Solubility; D013457:Sulfur Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013552:Swine; D029766:Terminalia / Q000737:chemistry; D013818:Thermogravimetry; D014867:Water; D014961:X-Ray Diffraction
D000473:Alkanes; D000893:Anti-Inflammatory Agents; D003505:Cyclodextrins; D004655:Emulsions; D005960:Glucosides; D010936:Plant Extracts; D013457:Sulfur Compounds; C421311:trithiacyclononane; D014867:Water; D009828:Oleanolic Acid; C479759:sericoside