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Effect of Auxiliary Substances on Complexation Efficiency and Intrinsic Dissolution Rate of Gemfibrozil–β-CD Complexes

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Abstract

The studies reported in this work are aimed to elucidate the ternary inclusion complex formation of gemfibrozil (GFZ), a poorly water-soluble drug, with β-cyclodextrin (β-CD) with the aid of auxiliary substances like different grades of povidone(s) (viz. PVP K-29/32, PVP K-40, Plasdone S-630, and Polyplasdone XL), organic base (viz. triethanolamine), and metal ion (viz. MgCl2·6H2O), by investigating their interactions in solution and solid state. Phase solubility studies were carried out to evaluate the solubilizing power of β-cyclodextrin, in association with various auxiliary substances, to determine the apparent stability constant (K C) and complexation efficiency (CE) of complexes. Improvement in K C values for ternary complexes clearly proves the benefit of the addition of auxiliary substances to promote CE. Of all the approaches used, the use of polymer Plasdone S-630 was found to be the most promising approach in terms of optimum CE and K C. GFZ–β-CD (1:1) binary and ternary systems were prepared by kneading and lyophilization methods. The ternary systems clearly signified superiority over binary systems in terms of CE, solubility, K C, and reduction in the formulation bulk. Optimized ternary system of GFZ–β-CD–Plasdone S-630 prepared by using lyophilization method indicated a significant improvement in intrinsic dissolution rate when compared with ternary kneaded system. Differential scanning calorimetry, X-ray diffraction, Fourier transform infrared, scanning electron microscopy, and proton nuclear magnetic resonance were carried out to characterize the binary and optimized ternary complex. The results suggested the formation of new solid phases, eliciting strong evidences of ternary inclusion complex formation between GFZ, β-CD, and Plasdone S-630, particularly for lyophilized products.

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Acknowledgements

The authors wish to thank IIT Delhi for providing the facilities for SEM and XRD. We would also like to thank Mr.Yogesh Murti and Mr. Harjeet Singh for their spectral suggestions.

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Authors and Affiliations

  1. Department of Pharmaceutics, Rajiv Academy for Pharmacy, Mathura, 286001, Uttar Pradesh, India

    Fareen Sami & Kamla Pathak

  2. Department of Pharmaceutics, David Memorial College of Pharmacy, Secunderabad-26, Andhra Pradesh, India

    Betty Philip

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  1. Fareen Sami
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Correspondence to Betty Philip.

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Sami, F., Philip, B. & Pathak, K. Effect of Auxiliary Substances on Complexation Efficiency and Intrinsic Dissolution Rate of Gemfibrozil–β-CD Complexes. AAPS PharmSciTech 11, 27–35 (2010). https://doi.org/10.1208/s12249-009-9350-y

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