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Advanced Formulation and Pharmacological Activity of Hydrogel of the Titrated Extract of C. Asiatica  

Hong Soon-Sun (Department of Pharmaceutics, College of Pharmacy, Seoul National University)
Kim Jong-Ho (Department of Pharmaceutics, College of Pharmacy, Seoul National University)
Li Hong (Department of Pharmaceutics, College of Pharmacy, Seoul National University)
Shim Chang-Koo (Department of Pharmaceutics, College of Pharmacy, Seoul National University)
Publication Information
Archives of Pharmacal Research / v.28, no.4, 2005 , pp. 502-508 More about this Journal
Abstract
Titrated extract of Centella asiatica (TECA) contains three principal ingredients, asiaticoside (AS), asiatic acid (AA), and madecassic acid (MA). These components are known to be clinically effective on systemic scleroderma, abnormal scar formation, and keloids. However, one problem associated with administration of TECA is its low solubility in aqueous as well as oil medium. In this study, various nonionic surfactants and bile salts as anionic surfactant were tested and screened for solubilizing TECA with a view to developing topical hydrogel type of ointment which is stable physicochemically, and has better pharmacological effects. When TECA was incorporated into various nonionic surfactant systems, labrasol had the most potent capacity for solubilizing TECA. In cases of bile salt systems, Na-deoxycholate (Na-DOC) had foremost solubilizing capacity, even more than labrasol. In differential scanning calorimetric study, the peaks of AA, MA, AS and Na-DOC disappeared at the coprecipitate of $1\%$ TECA and $1\%$ Na-DOC, suggesting the optimum condition of Na-DOC for solubilizing TECA. When the physicochemical stability of hydrogel containing this mixture was assessed, it was stable at room temperature for at least one month. Pharmacologically it significantly decreased the size of wound area at the $9^{th}$ day when applied to the wound area of rat dorsal skin. Taken together, solubility of TECA was dramatically improved by using non ionic and anionic surfactant systems, and Na-DOC was found to be the most effective solubilizer of TECA in formulating a TECA-containing hydrogel typed ointment. Moreover this gel was considered to be applicable to clinical use for wound healing effect.
Keywords
Centella asiatica; Asiatic acid; Asiaticoside; Madecassic acid; Bile salt; Hydrogel;
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Times Cited By Web Of Science : 13  (Related Records In Web of Science)
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1 Habibipour, S., Oswald, T. M., Zhang, F., Joshi, P., Zhou, X. C., Dorsett-Martin, W., and Lineaweaver, W. C., Effect of sodium diphenylhydantoin on skin wound healing in rats. Plast. Reconstr. Surg., 112, 1620-1627 (2003)   DOI   ScienceOn
2 Alvarez-Lorenzo, C., and Concheiro, A., Effects of surfactants on gel behavior: design implications for drug delivery systems. Am. J. Drug Deliv., 1, 77-101 (2003)   DOI   ScienceOn
3 Barreiro-Iglesias, R., Bromberg, L., Temchenko, M., Hatton and T. A., Concheiro, A., and Alvarez-Lorenzo, C., Solubilization and stabilization of camptothecin in micellar solutions of pluronic-g-poly(acrylic acid) copolymers. J. Control. Release, 97, 537-549 (2004)   DOI
4 Maquart, F. X., Chastang, F., Simeon, A., Birembaut, P., Gillery, P., and Wegrowski, Y., Triterpenes from Centella asiatica stimulate extracellular matrix accumulation in rat experimental wounds. Eur. J. Dermatol., 9(4), 289-296 (1999)
5 Patton, J. N. and Palmer, A. F., Photopolymerization of bovine hemoglobin entrapped nanoscale hydrogel particles within liposomal reactors for use as an artificial blood substitute. Biomacromolecules, 6, 414-424 (2005)   DOI   ScienceOn
6 Kiessetter, H., Report on experience in treating wounds with asiaticoside (madecassol). Wien Med. Wochenschr., 114, 124-126 (1964)
7 Islam M. T., Rodriguez-Hornedo, N., Ciotti, S., and Ackermann, C., The potential of Raman spectroscopy as a process analytical technique during formulations of topical gels and emulsions. Pharm. Res., 21, 1844-1851 (2004)   DOI   ScienceOn
8 Beljanski, M. and Vapaille, N., Role of triterpenes in the binding of L-amino acids by matricial RNA. Eur. Etud. Clin. Biol., 16, 897-905 (1971)
9 Malmsten, M., Surfactants and Polymers in Drug Delivery. Marcel Dekker, New York, pp. 215–259, (2002)
10 Rosen, H., Blumenthal, A., and McCallum, J., Effect of asiaticoside on wound healing in the rat. Proc. Soc. Exp. Biol. Med., 125, 279-280 (1967)   DOI   PUBMED
11 Trotta, M, Gallarate, M., Carlotti, M. E., and Morel, S., Preparation of griseofulvin nanoparticles from water-dilutable microemulsions. Int. J. Pharm., 254, 235-242 (2003)   DOI   ScienceOn
12 Bonacucina, G., Martelli, S., and Palmieri, G. F., Rheological, mucoadhesive and release properties of Carbopol gels in hydrophilic cosolvents. Int. J. Pharm., 282, 115-130 (2004)   DOI   PUBMED   ScienceOn
13 Djordjevic, L., Primorac, M., Stupar, M., and Krajisnik D., Characterization of caprylocaproyl macrogolglycerides based microemulsion drug delivery vehicles for an amphiphilic drug. Int. J. Pharm., 271, 11-19 (2004)   DOI   PUBMED   ScienceOn
14 Wiedmann, T. S. and Kamel, L., Examination of the solubilization of drugs by bile salt micelles. J. Pharm. Sci., 91, 1743- 1764 (2002)   DOI   ScienceOn
15 Barreiro-Iglesias R, Alvarez-Lorenzo, C., and Concheiro, A., Controlled release of estradiol solubilized in carbopol/surfactant aggregates. J. Control Release, 93, 319-330 (2003)   DOI   ScienceOn
16 Maquart, F. X., Bellon, G., Gillery, P., et al. Stimulation of collagen synthesis in fibroblast cultures by a triterpene extracted from Centella asiatica. Connect. Tissue Res., 24, 107-120 (1990)   DOI   ScienceOn
17 Contreras, M. D. and Sanchez, R. Application of a factorial design to the study of specific parameters of a Carbopol ETD 2020 gel. Part I. Viscoelastic parameters. Int. J. Pharm., 234(1-2), 139-147 (2002)   DOI   PUBMED   ScienceOn
18 Liu, Z., Lu, W., Qian, L., Zhang, X., Zeng, P., and Pan, J., In vitro and in vivo studies on mucoadhesive microspheres of amoxicillin. J. Control Release., 102, 135-44 (2005)   DOI   ScienceOn
19 Ringel, Y., Somjen, G. J., Konikoff, F. M., Rosenberg, R., Michowitz, M., and Gilat, T., The effects of phospholipid molecular species on cholesterol crystallization in model biles: the influence of phospholipid head groups. Hepatol., 28, 1008-1014 (1998)   DOI   ScienceOn