Complex formation of sericoside with hydrophilic cyclodextrins: improvement of solubility and skin penetration in topical emulsion based formulations

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 55; no. 2; pp. 191 - 198
• Main Authors: Rode, T., Frauen, M., Müller, B.W., Düsing, H.J., Schönrock, U., Mundt, C., Wenck, H.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.03.2003; Elsevier Science
• Subjects: Administration, Topical; Alkanes - administration & dosage; Alkanes - chemistry; Alkanes - pharmacokinetics; Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacokinetics; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Calorimetry, Differential Scanning; Cyclodextrins - administration & dosage; Cyclodextrins - chemistry; Cyclodextrins - pharmacokinetics; Drug Stability; Emulsions; General pharmacology; Glucosides; Hydroxypropylated-β-cyclodextrin; Hydroxypropylated-γ-cyclodextrin; In Vitro Techniques; Inclusion complex formation; Medical sciences; Methylated-β-cyclodextrin; Oleanolic Acid - administration & dosage; Oleanolic Acid - analogs & derivatives; Oleanolic Acid - chemistry; Oleanolic Acid - pharmacokinetics; Percutaneous in vitro penetration; Permeability; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Plant Bark - chemistry; Plant Extracts - administration & dosage; Plant Extracts - chemistry; Plant Extracts - pharmacokinetics; Plant Roots - chemistry; Sericoside; Skin - metabolism; Solubility; Sulfur Compounds - administration & dosage; Sulfur Compounds - chemistry; Sulfur Compounds - pharmacokinetics; Swine; Terminalia - chemistry; Terminaliasericea extract; Thermogravimetry; Water; Water solubility; X-Ray Diffraction; γ-Cyclodextrin; Terminalia sericea extract; Inclusion complex formation; Percutaneous in vitro penetration; γ-Cyclodextrin; Methylated-β-cyclodextrin; Water solubility; Sericoside; Hydroxypropylated-γ-cyclodextrin; Hydroxypropylated-β-cyclodextrin; Methylated-β- cyclodextrin; Ester; Dicotyledones; Angiospermae; Ungulata; Stability; Pharmaceutical technology; Oligosaccharide; Antiinflammatory agent; Permeation; In vitro; Pig; Oleanane derivatives; Vertebrata; Cyclodextrin; Mammalia; Combretaceae; Animal; Triterpene; Dosage form; Spermatophyta; Skin; Artiodactyla; Inclusion compound
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/S0939-6411(02)00194-7

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 β- and γ-cyclodextrins in a molar ratio of 1.0:1.1. The complex of extract and cyclodextrin was equilibrated in water at 25 °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 β-cyclodextrin as well as γ-cyclodextrin derivatives was detectable using these three analytical tools; however, only complexes with γ-cyclodextrin derivatives showed stability upon storage after incorporation into topical o/w or w/o formulations. Furthermore, a T. sericea extract/γ-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.