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Soluplus-Solubilized Citrated Camptothecin—A Potential Drug Delivery Strategy in Colon Cancer

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Abstract

Camptothecin (CPT), a potent antitumor drug, exhibits poor aqueous solubility and rapid conversion from the pharmacologically active lactone form to inactive carboxylate form at physiological pH. Solid dispersion of CPT in Soluplus®, an amphiphilic polymeric solubilizer, was prepared to increase the aqueous solubility of CPT and the resultant solid dispersion along with citric acid was formulated as hard gelatin capsules that were subsequently coated with Eudragit S100 polymer for colonic delivery. FTIR spectrum of the solid dispersion confirmed the presence of CPT. PXRD and DSC revealed the semicrystalline nature of solid dispersion. The solubility of the drug was found to increase ~40 times in the presence of Soluplus and ~75 times in solid dispersion. The capsules showed no drug release in 0.01 N HCl but released 86.4% drug in lactone form in phosphate buffer (pH 7.4) and the result appears to be due to citric acid-induced lowering of pH of buffer from 7.4 to 6.0. Thus the presence of citric acid in the formulation led to stabilization of the drug in its pharmacologically active lactone form. Cytotoxicity studies conducted with the formulation of solid dispersion with citric acid, utilizing cell cytotoxicity test (MTT test) on Caco-2 cells, confirmed cytotoxic nature of the formulation.

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Authors and Affiliations

  1. Centre for Biomedical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, 110016, India

    Naveen K. Thakral & Alok R. Ray

  2. Biomedical Engineering Unit, All India Institute of Medical Science, New Delhi, 110029, India

    Alok R. Ray

  3. Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken-2, 2100, Copenhagen, Denmark

    Daniel Bar-Shalom

  4. Bioneer:FARMA, Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken-2, 2100, Copenhagen, Denmark

    André Huss Eriksson

  5. Department of Pharmaceutics, Delhi Institute of Pharmaceutical Sciences and Research, Formerly College of Pharmacy, University of Delhi, Pushp Vihar, Sector III, New Delhi, 110017, India

    Dipak K. Majumdar

Authors
  1. Naveen K. Thakral
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  2. Alok R. Ray
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  3. Daniel Bar-Shalom
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  4. André Huss Eriksson
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  5. Dipak K. Majumdar
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Correspondence to Dipak K. Majumdar.

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Thakral, N.K., Ray, A.R., Bar-Shalom, D. et al. Soluplus-Solubilized Citrated Camptothecin—A Potential Drug Delivery Strategy in Colon Cancer. AAPS PharmSciTech 13, 59–66 (2012). https://doi.org/10.1208/s12249-011-9720-0

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  • DOI: https://doi.org/10.1208/s12249-011-9720-0

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