Hydroxypropyl-β-cyclodextrin Inclusion Complexes for Transdermal Delivery: Preparation, Inclusion Properties, Stability, and Release Behavior

Seung Hei; So Yeon Kim; Sang In Lee; Young Moo Lee

Journal of Industrial and Engineering Chemistry, Vol.12, No.1, 50-59, January, 2006

Seung Hei, So Yeon Kim, Sang In Lee¹, and Young Moo Lee^†

School of Chemical Engineering, College of Engineering, Hanyang University, Seoul 133-791, Korea
¹Macrocare Tech., Lte,, Ochang-myeon, Cheongwon-gun, Chungbuk 363-883, Korea

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Hydroxypropyl-β-cyclodextrin (HPCD), a highly water-soluble derivative, was synthesized by the substitution of the hydroxyl groups in the glucopyranose units of β-cyclodextrin (β-CD) with hydroxypropyl groups to improve its solubility in aqueous solution and its biocompatibility. β-CD has only limited water solubility (~1.8 g/mL at ambient temperature), whereas HPCD showed high water solubility and also dissolved in solvents such as methanol, ethanol, DMF, and DMSO. To investigate their feasibility for transdermal delivery applications, HPCD inclusion complexes containing several lipophilic guest molecules (retinol, tocopherol, and genistein) were prepared through complex formation by taking advantage of the special molecular structure of HPCD, which has a hydrophobic interior cavity and a hydrophilic exterior. The molar inclusion efficiency of guest molecules within HPCD was ca. 8~12 % when the feed molar ratio of guest molecules to CD was 1. The inclusion efficiency was influenced by the feed molar ratio and by the type of guest molecule. The stabilities of the inclusion complexes were investigated with respect to the temperature, pH, and solvent. HPCD complexes exhibited enhanced stability in comparison with those of the parent β-CD. From an in vitro skin permeation study using a Frantz diffusion cells, ca. 70~90 % permeation of guest molecules was observed within 7 days.

Keywords:hydroxypropyl-β-cyclodextrin;β-cyclodextrin;water solubility;vitamin;inclusion complex

[References]

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Lindberg B, Lindberg J, Carbohydr. Res., 222, 113 (1991)
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Lupo MP, Clin. Dermatol., 19, 467 (2001)
Failloux N, Bonnet I, Perrier E, Baron MH, J. Raman Spectrosc., 35, 140 (2004)
Lee JS, Nam YS, Kang BY, Han SH, Chang IS, J. Appl. Polym. Sci., 92(1), 517 (2004)
Scalia S, Renda A, Ruberto G, Bonina F, Menegatti E, J. Pharm. Biomed. Anal., 13, 273 (1995)
McClain RM, Wolz E, Davidovich A, Pfannkuch F, Bausch J, Food Chem. Toxicol., 43, 1461 (2005)
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Pitha J, Rao C Lindberg B, Seffers P, Carbohydr. Res., 200, 429 (1990)
Reuben J, Rao CT, Pitha J, Carbohydr. Res., 258, 281 (1994)
Van Santvliet L, Caljon K, Pieters L, Ludwig A, Int. J. Pharm., 171, 147 (1998)
Amnuaikit C, Ikeuchi I, Ogawara K, Higaki K, Kimura T, Int. J. Pharm., 289, 167 (2005)
Yue IC, Poff J, Cortes ME, Sinisterra RD, Faris CB, Hildgen P, Langer R, Shastri VP, Biomaterials, 25, 3743 (2004)
Cerchiara T Luppi B, Bigucci F, Zecchi V, Int. J. Pharm., 258, 209 (2003)

[Referenced By]

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[1] Atwood JL, Davis JED, MacNicol DD, Vogtle F, Lehn JM, Szejtli J. Osa, Comperhensive supramolecular chemistry, Volume 3. Elsevier Science, New York (1996)

[2] Martin Del Valle EM, Process Biochem., 39, 1033 (2004)

[3] Singh Sharma M, Banerjee UC, Biotechnol. Adv., 20, 341 (2002)

[4] Gattuso G, Nepogodiev SA, Stoddart JF, Chem. Rev., 98(5), 1919 (1998)

[5] Matsuda H, Arima H, Adv. Drug Deliv. Rev., 36, 81 (1999)

[6] Rajewski RA, Stella VJ, J. Pharm. Sci., 85, 1142 (1996)

[7] Szente L, Szejtli J, Adv. Drug Deliv. Rev., 36, 17 (1999)

[8] Lindberg B, Lindberg J, Carbohydr. Res., 222, 113 (1991)

[9] Jambhekar S, Casella R, Maher T, Int. J. Pharm., 270, 149 (2004)

[10] Manosroi J, Apriyani MG, Foe K, Manosroi A, Int. J. Pharm., 293, 235 (2005)

[11] Wenz G, Hofler T, Carbohydr. Res., 322, 153 (1999)

[12] Shuang S, Choi MMF, J. Chromatogr. A, 919, 321 (2001)

[13] Sabah S, Scriba GKE, J. Chromatogr. A, 833, 261 (1999)

[14] Lupo MP, Clin. Dermatol., 19, 467 (2001)

[15] Failloux N, Bonnet I, Perrier E, Baron MH, J. Raman Spectrosc., 35, 140 (2004)

[16] Lee JS, Nam YS, Kang BY, Han SH, Chang IS, J. Appl. Polym. Sci., 92(1), 517 (2004)

[17] Scalia S, Renda A, Ruberto G, Bonina F, Menegatti E, J. Pharm. Biomed. Anal., 13, 273 (1995)

[18] McClain RM, Wolz E, Davidovich A, Pfannkuch F, Bausch J, Food Chem. Toxicol., 43, 1461 (2005)

[19] Yu Z, Tang Y, Hu D, Li J, Biochem. Biophys. Res. Commun., 333, 827 (2005)

[20] Pitha J, Rao C Lindberg B, Seffers P, Carbohydr. Res., 200, 429 (1990)

[21] Reuben J, Rao CT, Pitha J, Carbohydr. Res., 258, 281 (1994)

[22] Van Santvliet L, Caljon K, Pieters L, Ludwig A, Int. J. Pharm., 171, 147 (1998)

[23] Amnuaikit C, Ikeuchi I, Ogawara K, Higaki K, Kimura T, Int. J. Pharm., 289, 167 (2005)

[24] Yue IC, Poff J, Cortes ME, Sinisterra RD, Faris CB, Hildgen P, Langer R, Shastri VP, Biomaterials, 25, 3743 (2004)

[25] Cerchiara T Luppi B, Bigucci F, Zecchi V, Int. J. Pharm., 258, 209 (2003)