Skip to main content
SpringerLink
Log in

Influence of Microcrystal Formulation on In Vivo Absorption of Celecoxib in Rats

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The objective of this study was to prepare celecoxib microcrystals using different stabilizers in order to evaluate the influence of microcrystal formulation on the in vitro dissolution rate and in vivo absorption after oral administration of celecoxib in rats. Three celecoxib microcrystals (MC1, MC2, and MC3) were prepared using solvent change method. Microcrystals were evaluated for morphology, particle size, crystallinity, solubility, in vitro dissolution, and in vivo absorption in rats. Scanning electron microscopy images showed distinct differences in the morphologies and dimensions of various celecoxib microcrystals. The particle size of all microcrystals was significantly (P < 0.05) reduced relative to plain celecoxib. The DSC and XRD results revealed that MC1 retain drug crystallinity relative to control crystals, MC2, and MC3. All microcrystals showed marked increase in the drug dissolution parameters particularly MC1 that exhibited a prompt drug release and significantly (P < 0.05) higher values of % dissolution efficiency as compared to control celecoxib and the other microcrystals. The influence of microcrystals on the in vivo absorption of celecoxib was studied in rats in comparison to plain drug. The results of in vivo absorption study in rats indicated that MC1 significantly improved the rate and extent of celecoxib absorption than plain celecoxib. The mean relative bioavailability of MC1 formulation to plain celecoxib was 157.55 ± 20.18%. In conclusion, microcrystal formulation of celecoxib results not only in an enhancement of dissolution parameters but also improves the bioavailability of celecoxib in rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Davies NM, McLachlan AJ, Day RO, Williams KM. Clinical pharmacokinetics and pharmacodynamics of celecoxib: a selective cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet. 2000;38:225–42.

    Article  CAS  PubMed  Google Scholar 

  2. Löbenberg R, Amidon GL. Modern bioavailability, bioequivalence and biopharmaceutics classification system. New scientific approaches to international regulatory standards. Eur J Pharm Biopharm. 2000;50:3–12.

    Article  PubMed  Google Scholar 

  3. Tan A, Simovic S, Davey AK, Rades T, Prestidge CA. Silica-lipid hybrid (SLH) microcapsules: a novel oral delivery system for poorly soluble drugs. J Control Release. 2009;134:62–70.

    Article  CAS  PubMed  Google Scholar 

  4. Reddy MN, Rehana T, Ramakrishna S, Chowdary KPR, Diwan PV. Β cyclodextrin complexes of celecoxib: molecular-modeling characterization, and dissolution studies. AAPS PharmSci. 2004;6(1):1–9.

    Article  Google Scholar 

  5. Orienti I, Bigucci F, Luppi B, Cerchiara T, Zuccari G, Giunchedi P, et al. Polyvinylalcohol substituted with triethyleneglycolmonoethyl ether as a new material for preparation of solid dispersion of hydrophobic drugs. Eur J Pharm Biopharm. 2002;54:229–33.

    Article  CAS  PubMed  Google Scholar 

  6. Paulson SK, Vaughn MB, Jessen SM, Lawal Y, Gresk CJ, Yan B, et al. Pharmacokinetics of celecoxib after oral administration in dogs and humans: effect of food and site of absorption. J Pharmacol Exp Ther. 2001;297:638–45.

    CAS  PubMed  Google Scholar 

  7. Shono Y, Jantratid E, Janssen N, Kesisoglou F, Mao Y, Vertzoni M, et al. Prediction of food effects on the absorption of celecoxib based on biorelevant dissolution testing coupled with physiologically based pharmacokinetic modeling. Eur J Pharm Biopharm. 2009;73:107–14.

    Article  CAS  PubMed  Google Scholar 

  8. Dressmann JB, Reppas C. In vitro–in vivo correlations for lipophilic, poorly water soluble drugs. Eur J Pharm Sci. 2000;11:73–80.

    Article  Google Scholar 

  9. Sarkari M, Brown J, Chen X, Swinnea S, William RO, Johnston KP. Enhanced drug dissolution using evaporative precipitation into aqueous solution. Int J Pharm. 2002;243:17–31.

    Article  CAS  PubMed  Google Scholar 

  10. Kesisoglou F, Panmai S, Wu Y. Nanosizing-oral formulation development and biopharmaceutical evaluation. Adv Drug Deliv Rev. 2007;5916:31–44.

    Google Scholar 

  11. Rasenack N, Steckel H, Müller BW. Preparation of microcrystals by in situ micronization. Powder Technol. 2004;143–144:291–6.

    Article  Google Scholar 

  12. Rasenack N, Müller BW. Dissolution rate enhancement by in situ micronization of poorly water-soluble drugs. Pharm Res. 2002;19:1894–900.

    Article  CAS  PubMed  Google Scholar 

  13. Kim ST, Kwon JH, Lee JJ, Kim CW. Microcrystallization of indomethacin using a pH-shift method. Int J Pharm. 2003;263:141–50.

    Article  CAS  PubMed  Google Scholar 

  14. Williams 3rd RO, Brown J, Liu J. Influence of micronization method on the performance of a suspension triamcinolone acetonide pressurized metered-dose inhaler formulation. Pharm Dev Technol. 1999;4(2):167–79.

    Article  CAS  PubMed  Google Scholar 

  15. Zhang HX, Wang JX, Zhang ZB, Le Y, Shen ZG, Chen JF. Micronization of atorvastatin calcium by antisolvent precipitation process. Int J Pharm. 2009;374(1–2):106–13.

    Article  CAS  PubMed  Google Scholar 

  16. Huang QP, Wang JX, Chen GZ, Shen ZG, Chen JF, Yun J. Micronization of gemfibrozil by reactive precipitation process. Int J Pharm. 2008;360:58–64.

    Article  CAS  PubMed  Google Scholar 

  17. Gupta VR, Mutalik S, Patel MM, Jani GK. Spherical crystals of celecoxib to improve solubility, dissolution rate and micromeritic properties. Acta Pharma. 2007;57:173–84.

    CAS  Google Scholar 

  18. Dolenc A, Kristl J, Baumgartner S, Planinsek O. Advantages of celecoxib nanosuspension formulation and transformation into tablets. Int J Pharm. 2009;376:204–12.

    Article  CAS  PubMed  Google Scholar 

  19. Margulis-Goshen K, Kesselman E, Danino D, Magdassi S. Formation of celecoxib nanoparticles from volatile microemulsions. Int J Pharm. 2010;393:230–7.

    Article  CAS  PubMed  Google Scholar 

  20. Rasenack N, Hartenhauer H, Müller BW. Microcrystals for dissolution rate enhancement of poorly water-soluble drugs. Int J Pharm. 2003;254:137–45.

    Article  CAS  PubMed  Google Scholar 

  21. Liu Y, Sun C, Haob Y, Jiang T, Zheng L, Wang S. Mechanism of dissolution enhancement and bioavailability of poorly water soluble celecoxib by preparing stable amorphous nanoparticles. J Pharm Pharm Sci. 2010;13(4):589–606.

    CAS  PubMed  Google Scholar 

  22. Niederberger E, Tegeder I, Vetter G, Schmidtko A, Schmidt H, Euchenhofer C, et al. Celecoxib loses its anti-inflammatory efficacy at high doses through activation of NF kappa B. FASEB J. 2001;15(9):1622–4.

    CAS  PubMed  Google Scholar 

  23. Park MS, Shim WS, Yim SV, Lee KT. Development of simple and rapid LC-MS/MS method for determination of celecoxib in human plasma and its application to bioequivalence study. J Chromatogr B Anal Technol Biomed Life Sci. 2012;902:137–41.

    Article  CAS  Google Scholar 

  24. U.S. Food and Drug Administration. Title 21 Code of Federal Regulations (CFR), Part 320.1. Washington, DC: Office of Federal Register, National Archives and Records Administration, U.S. Government Printing Office; 2010.

    Google Scholar 

  25. Zhang JY, Shen ZG, Zhong J, Hu TT, Chen JF, Ma ZQ, et al. Preparation of amorphous cefuroxime axetil nanoparticles by controlled nano-precipitation method without surfactants. Int J Pharm. 2006;323:153–60.

    Article  CAS  PubMed  Google Scholar 

  26. Chawla G, Gupta P, Thilagavathi R. Characterization of solid-state forms of celecoxib. Eur J Pharm Sci. 2003;20:305–17.

    Article  CAS  PubMed  Google Scholar 

  27. Varshosaz J, Talari R, Mostafavi SA, Nokhodchi A. Dissolution enhancement of gliclazide using in situ micronization by solvent change method. Powder Technol. 2008;187:222–30.

    Article  CAS  Google Scholar 

  28. Zhong J, Shen Z, Yang Y, Chen J. Preparation and characterization of uniform nanosized cephradine by combination of reactive precipitation and liquid anti-solvent precipitation under high gravity environment. Int J Pharm. 2005;301:286–93.

    Article  CAS  PubMed  Google Scholar 

  29. Khan KA. The concept of dissolution efficiency. J Pharm Pharmacol. 1975;28:48–9.

    Article  Google Scholar 

  30. Li XS, Wang JX, Shen ZG, Zhang PY, Chen JF, Yun J. Preparation of uniform prednisolone microcrystals by a controlled microprecipitation method. Int J Pharm. 2007;342:26–32.

    Article  CAS  PubMed  Google Scholar 

  31. Noyes AA, Whitney WR. The rate of solution of solid substances in their own solutions. J Am Chem Soc. 1897;19:930–4.

    Article  Google Scholar 

Download references

Acknowledgments

The author thanks Sedico pharmaceutical Co. for kindly supplying celecoxib powder.

Author information

Authors and Affiliations

  1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Cairo, Egypt

    Mohamed Nasr

Authors
  1. Mohamed Nasr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohamed Nasr.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nasr, M. Influence of Microcrystal Formulation on In Vivo Absorption of Celecoxib in Rats. AAPS PharmSciTech 14, 719–726 (2013). https://doi.org/10.1208/s12249-013-9957-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-013-9957-x

KEY WORDS

Search

Navigation