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Stabilization and Improved in Vivo Performance of Amorphous Etoricoxib using Gelucire 50/13

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Purpose

Amorphous drugs have gained importance because of their advantageous biopharmaceutical properties; however, their stabilization remains a challenge. The purpose of this work was to stabilize the amorphous form of etoricoxib (ET) by using a low excipient/drug ratio to improve drug dissolution and thus bioavailability.

Methods

The effect of Gelucire and polyvinylpyrrolidone (PVP) on stabilization and bioavailability of amorphous etoricoxib (AET) was studied. X-ray powder diffractometry, differential scanning calorimetry, and scanning electron microscopy were used to study the physical state of the drug. Dissolution studies were performed for melt granules of AET with Gelucire 50/13 (MG-AET) and solid dispersion with PVP (SDP) to differentiate dissolution performance. A stability study on samples was conducted for 3 months to evaluate the physical state of the drug and its dissolution in the formulation. The in vivo performance of the optimized and stable formulation of ET was evaluated in rat.

Results

Dissolution of MG-AET was significantly improved as compared to AET and SDP. Both factors, amorphization of drug and melt granulation with lipid, seemed to be important for improving dissolution. Stability data revealed that MG-AET was significantly advantageous for AET stabilization, whereas PVP was not. The amount of Gelucire required for the stabilization of one part of AET was 0.5 part (by weight), whereas even 1.5 part (by weight) of PVP failed to elicit the same result. The superior in vivo performance of MG-AET has been attributed to the altered physiochemical properties of AET and the presence of lipid in the system.

Conclusion

Gelucire can stabilize AET and improve its biopharmaceutical performance at a low excipient/drug ratio and may provide a better alternative to conventional stabilizers such as PVP.

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Abbreviations

AET:

amorphous etoricoxib

AUC:

area under curve

BA:

bioavailability

C max :

maximum concentration

ET:

etoricoxib

HPLC:

high-pressure liquid chromatography

MG-AET:

melt granulation of AET with lipid

MG-CET:

melt granulation of crystalline ET with lipid

PVP:

polyvinylpyrrolidone

SD:

solid dispersions

SDL:

solid dispersion with lipid

SDP:

solid dispersion with PVP

T g :

glass transition temperature

T max :

time at which maximum concentration is reached

ΔH:

heat of melting

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Acknowledgments

The authors wish to thank UGC (New Delhi, India) for its support of this study under Major Research Project and Special Assistant Programme. S.L. Shimpi is grateful to CSIR (New Delhi, India) for financial support in terms of a Senior Research Fellowship. The authors are also thankful to Dr. Prashant Kharkar for fruitful discussions on molecular modeling, and wish to acknowledge Gattefosse (France) and Colorcon (India) for providing the Gelucire as a gift.

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Authors and Affiliations

  1. Department of Pharmaceutics, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane Pune, 411 038, Maharashtra, India

    Shamkant L. Shimpi, Bhaskar Chauhan, K. R. Mahadik & Anant Paradkar

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  1. Shamkant L. Shimpi
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  2. Bhaskar Chauhan
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  3. K. R. Mahadik
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  4. Anant Paradkar
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Correspondence to Anant Paradkar.

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Shimpi, S.L., Chauhan, B., Mahadik, K.R. et al. Stabilization and Improved in Vivo Performance of Amorphous Etoricoxib using Gelucire 50/13. Pharm Res 22, 1727–1734 (2005). https://doi.org/10.1007/s11095-005-6694-1

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  • DOI: https://doi.org/10.1007/s11095-005-6694-1

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