J Cancer 2017; 8(6):913-923. doi:10.7150/jca.17301 This issue

Research Paper

Super Aqueous Solubility of Albendazole in β-Cyclodextrin for Parenteral Application in Cancer therapy

Krishna Pillai, Javed Akhter, David Lawson Morris

Department of Surgery, University of New South Wales, St. George Hospital, Kogarah, NSW, Australia

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Pillai K, Akhter J, Morris DL. Super Aqueous Solubility of Albendazole in β-Cyclodextrin for Parenteral Application in Cancer therapy. J Cancer 2017; 8(6):913-923. doi:10.7150/jca.17301. Available from https://www.jcancer.org/v08p0913.htm

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Poor aqueous solubility of anticancer drug, albendazole (ABZ), prevents parenteral application. Here, we demonstrate how to increase the aqueous solubility of ABZ to 6- 8 mg/ml using sulfobutylether - β-cyclodextrin (SBE-β-CD) or Hydroxypropyl- β-cyclodextrin (HP- β-CD) by manipulation of complexation parameters such as the physical state of ABZ (ionized in acetic acid), the concentration of ionised ABZ, agitation time and temperature. Solubility was first examined with suspension of excess ABZ powder in cyclodextrin (CD) solutions at pH (2.3, 4.0 & 7.0), subsequently with excess ionised ABZ [ABZ] at pH. 2.3 with the determination of optimal quantity of [ABZ] use for maximal complexation. Complexation time, temperature effect, stability of formulation, with in vitro and in vivo cytotoxicity of [ABZ]-SBE-β-CD was assessed. Suspended ABZ formulation at pH 2.3 showed maximum solubilisation of 2.29 & 1.72 mg/ml, whilst excess addition of [ABZ] showed poor complexation (1.26 & 1.20 mg/ml) in SBE-β-CD & HP- β-CD, respectively. The addition of 8.0 mg/ml and 7.0 mg/ml of [ABZ] to 40% CD solutions at 25ºC showed maximum complexation with SBE-β-CD & HP- β-CD, respectively, at three days, with 2 weeks stability. [ABZ] complexed with SBE-β-CD showed potent cytotoxicity (in vitro & in vivo) in ovarian tumour cells. Hence, the current method may be used for solubilising ABZ for parenteral use.

Keywords: Albendazole, aqueous, solubility, cyclodextrin, complexation, cytotoxicity.