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Preparation, characterization and pharmacodynamic activity of supramolecular and colloidal systems of rosuvastatin–cyclodextrin complexes

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Abstract

In the present study influence of nature of selected cyclodextrins (CDs) and of methods of preparation of drug–CD complexes on the oral bioavailability, in vitro dissolution studies and pharmacodynamic activity of a sparingly water soluble drug rosuvastatin (RVS) was investigated. Phase solubility studies were conducted to find the interaction of RVS with β-CD and its derivatives, which indicated the formation of 1:1 stoichiometric inclusion complex. The apparent stability constant (K1:1) calculated from phase solubility diagram were in the rank order of β-CD < hydroxypropyl-β-cyclodextrin (HP-β-CD) < randomly methylated-β-cyclodextrin (RM-β-CD). Equimolar drug–CD solid complexes prepared by different methods were characterized by the Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). FTIR study demonstrated the presence of intermolecular hydrogen bonds and ordering of the molecule between RVS and CDs in inclusion complexes. DSC and XRD analysis confirmed formation of inclusion complex by freeze dried method with HP-β-CD and RM-β-CD. Aqueous solubility and dissolution studies indicated improved dissolution rates of prepared complexes in comparison with drug alone. Moreover, CD complexes demonstrated of significant improvement in reducing total cholesterol and triglycerides levels as compared to pure drug. However the in vivo results only partially agreed with those obtained from phase solubility studies.

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Abbreviations

CDs:

Cyclodextrins

RVS:

Rosuvastatin

β-CD:

β-cyclodextrin

HP-β-CD:

Hydroxypropyl-β-cyclodextrin

RM-β-CD:

Randomly methylated-β-cyclodextrin

KND:

Kneading

PM:

Physical mixtures

COEVP:

Coevaporation

FZD:

Freeze dried

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Acknowledgment

The authors are thankful to UGC SAP, New Delhi for financial assistance. Authors are grateful to Ranbaxy, India for providing pure drug, Dr. Denis Simon and Emilie Van Oudendycke of Roquette, Lestrem, France and Signet Chemical Corpn. Pvt. Ltd. Mumbai, India for providing β-cyclodextrin, hydroxypropyl-beta-cyclodextrin, randomly methylated-β-cyclodextrin. Authors also extend their gratitude to Head, University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India for providing facilities to carry out research work.

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  1. University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur, 492010, Chhattisgarh, India

    Amber Vyas

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Vyas, A. Preparation, characterization and pharmacodynamic activity of supramolecular and colloidal systems of rosuvastatin–cyclodextrin complexes. J Incl Phenom Macrocycl Chem 76, 37–46 (2013). https://doi.org/10.1007/s10847-012-0170-4

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