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Sulfobutyl Ether7 β-Cyclodextrin (SBE7 β-CD) Carbamazepine Complex: Preparation, Characterization, Molecular Modeling, and Evaluation of In Vivo Anti-epileptic Activity

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Abstract

The objective of the present investigation was to study the ability of sulfobutyl ether7-β-cyclodextrin to form an inclusion complex with carbamazepine, an anti-epileptic drug with poor water solubility. The formation of the complex was carried out using the industrially feasible spray-drying method. The inclusion complex and physical mixtures were characterized by various techniques such as differential scanning calorimetry (DSC), infrared (IR), nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and molecular modeling. The DSC, IR, and NMR studies confirmed the formation of an inclusion complex between carbamazepine and sulfobutyl ether7 β-cyclodextrin whereas XRD studies indicated an amorphous nature of the inclusion complex. Molecular modeling studies disclosed different modes of interaction between carbamazepine and sulfobutyl ether7 β-cyclodextrin with good correlation with experimental observations. The inclusion complex exhibited significantly higher in vitro dissolution profile as compared with pure carbamazepine powder. The in vivo anti-epileptic activity of carbamazepine/sulfobutyl ether7 β-cyclodextrin complex was evaluated in pentylenetetrazole-induced convulsions model. The carbamazepine/sulfobutyl ether7 β-cyclodextrin complex showed significantly higher anti-epileptic activity (p <0.01) as compared with that of carbamazepine suspension on oral administration.

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Acknowledgments

Authors are thankful to Novartis India Ltd., for the gift sample of carbamazepine and to Signette Chemicals, Mumbai, India for the gift samples of lactose. The authors would also like to thank Mr. Nimish Vador and Dr. Aarati Jagtap, Department of Pharmacology, Bombay College of Pharmacy for useful suggestions and help while conducting animal studies. The NMR and XRD facility provided by the Tata Institute of Fundamental Research, Mumbai is gratefully acknowledged. A. Jain is thankful to AICTE for Junior Research Fellowship and A. Date is thankful to Indian Council of Medical Research for Senior Research Fellowship. The computational facilities supported by the Department of Biotechnology (BT/TF-8/BRB/2009), Council for Scientific and Industrial Research (file no. 01/2399/10/EMRII), and Department of Science and Technology (SR/FST/LSI-163/2003), New Delhi, are gratefully acknowledged.

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Authors and Affiliations

  1. Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (East), Mumbai, 400098, India

    Ankitkumar S. Jain, Abhijit A. Date & Mangal S. Nagarsenker

  2. Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina, Santacruz (East), Mumbai, 400098, India

    Raghuvir R. S. Pissurlenkar & Evans C. Coutinho

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  1. Ankitkumar S. Jain
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  2. Abhijit A. Date
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  4. Evans C. Coutinho
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  5. Mangal S. Nagarsenker
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Correspondence to Mangal S. Nagarsenker.

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Jain, A.S., Date, A.A., Pissurlenkar, R.R.S. et al. Sulfobutyl Ether7 β-Cyclodextrin (SBE7 β-CD) Carbamazepine Complex: Preparation, Characterization, Molecular Modeling, and Evaluation of In Vivo Anti-epileptic Activity. AAPS PharmSciTech 12, 1163–1175 (2011). https://doi.org/10.1208/s12249-011-9685-z

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