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Kneading Technique for Preparation of Binary Solid Dispersion of Meloxicam with Poloxamer 188

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Abstract

The aim of the present study was to enhance the dissolution rate of meloxicam (MLX), a practically water-insoluble drug by preparation of solid dispersion using a hydrophilic polymer, poloxamer 188 (PXM). The kneading technique was used to prepare solid dispersions. A 32 full factorial design approach was used for optimization wherein the drug, polymer ratio (X 1), and the kneading time (X 2) were selected as independent variables and the dissolution efficiency at 60 min (%DE60) and yield percent were selected as the dependent variable. Multiple linear regression analysis revealed that for obtaining higher dissolution of MLX from PXM solid dispersions, a high level of X 1 and a high level of X 2 were suitable. The use of a factorial design approach helped in optimization of the preparation and formulation of solid dispersion. The optimized formula was characterized by solubility studies, angle of repose, and contact angle; Fourier transform infrared spectroscopy, differential scanning calorimetry, x-ray diffraction studies, and scanning electron microscopy demonstrated that enhanced dissolution of MLX from solid dispersion might be due to a decrease in the crystallinity of MLX and PXM. Analysis of dissolution data of optimized formula indicated the best fitting with Korsemeyer–Peppas model and the drug release kinetics as Fickian diffusion. In conclusion, dissolution enhancement of MLX was obtained by preparing its solid dispersion with PXM using kneading technique.

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References

  1. Pairet M, van Ryn J, Schierok H, Mauz A, Trummlitz G, Engelhardt G. Differential inhibition of cyclooxygenases-1 and -2 by meloxicam and its 40-isomer. Inflamm Res. 1998;47(6):270–6.

    Article  CAS  PubMed  Google Scholar 

  2. Lugar P, Daneck K, Engel W, Trummlitz G, Wagner K. Structure and physicochemical properties of meloxicam, a new NSAID. Eur J Pharm Sci. 1996;4:175–87.

    Article  Google Scholar 

  3. Lipscomb GR, Wallis N, Armstrong G, Rees WD. Gastrointestinal tolerability of meloxicam and piroxicam: a double-blind placebo-controlled study. Br J Clin Pharmacol. 1998;46(2):133–7.

    Article  CAS  PubMed  Google Scholar 

  4. Türck D, Roth W, Busch U. A review of the clinical pharmacokinetics of meloxicam. Br J Rheumatol. 1996;35(Suppl 1):13–6.

    PubMed  Google Scholar 

  5. Naidu NB, Chowdary KP, Murthy KV, Satyanarayana V, Hayman AR, Becket G. Physicochemical characterization and dissolution properties of meloxicam-cyclodextrin binary systems. J Pharm Biomed Anal. 2004;35(1):75–86.

    Article  CAS  PubMed  Google Scholar 

  6. Vijaya Kumar SG, Mishra DN. Preparation and evaluation of solid dispersion of meloxicam with skimmed milk. Yakugaku Zasshi. 2006;126(2):93–7.

    Article  PubMed  Google Scholar 

  7. Vijaya Kumar SG, Mishra DN. Preparation, characterization and in vitro dissolution of solid dispersion of meloxicam with PEG6000. Yakugaku Zasshi. 2006;126(8):657–64.

    Article  PubMed  Google Scholar 

  8. Collett JH, Popli H, Kibbe AH, editors. Poloxamer. In: Handbook of Pharmaceutical Excipients, 3rd ed. London, UK: Pharmaceutical Press; 2000. p. 386–8.

  9. Hang Y, Myung-Kwan C, Hoo-Kyun C. Preparation and characterization of piroxicam/poloxamer solid dispersion prepared by melting method and solvent method. J Korean Pharm Sci. 2007;37:1–5.

    Article  Google Scholar 

  10. Chutimaworapan S, Ritthidej GC, Yonemochi E, Oguchi T, Yamamoto K. Effect of water-soluble carriers on dissolution characteristics of nifedipine solid dispersions. Drug Dev Ind Pharm. 2000;26(11):1141–50.

    Article  CAS  PubMed  Google Scholar 

  11. Modi A, Tayade P. Enhancement of dissolution profile by solid dispersion (kneading) technique. AAPS PharmSciTech. 2006;7(3):68.

    Article  PubMed  Google Scholar 

  12. Elkheshen AS, Abdel-Gawad NA, Badawi AA. Factorial design and computer optimisation of a reconstitutable suspension of erythromycin ethyl succinate. Die Pharm Ind. 1997;59(5):439–43.

    CAS  Google Scholar 

  13. Higuchi T, Connors KA. “Phase-solubility techniques” in advances in analytical chemistry and instrumentation. New York: Reilly CN; 1965. p. 117–212.

    Google Scholar 

  14. Bolton S, Charles S. Pharmaceutical statistics. New York, NY: Marcel Dekker Inc.; 2004.

    Google Scholar 

  15. Chiou WL, Riegelman S. Pharmaceutical applications of solid dispersion systems. J Pharm Sci. 1971;60:1281–302.

    Article  CAS  PubMed  Google Scholar 

  16. Singh B, Kaur T, Singh S. Correction of raw dissolution data for loss of drug and volume during sampling. Indian J Pharm Sci. 1997;59:196–9.

    CAS  Google Scholar 

  17. Khan KA. The concept of dissolution efficiency. J Pharm Pharmacol. 1975;27:48–9.

    CAS  PubMed  Google Scholar 

  18. Gohel MC, Panchal MK. Novel use of similarity factor f2 and Sd for the development of diltiazem HCl modified-release tablets using a 32 factorial design. Drug Dev Ind Pharm. 2002;28:77–87.

    Article  CAS  PubMed  Google Scholar 

  19. McKenna A, McCafferty DF. Effect of particle size on the compaction mechanism and tensile strength of tablets. J Pharm Pharmacol. 1982;34(6):347–51.

    CAS  PubMed  Google Scholar 

  20. Imai T, Nishiyama T, Ueno M, Otagiri M. Enhancement of the dissolution rates of poorly water-soluble drugs by water-soluble gelatin. Chem Pharm Bull. 1989;37(8):2251–2.

    CAS  PubMed  Google Scholar 

  21. Merchant HA, Shoaib HM, Tazeen J, Yousuf RI. Once-daily tablet formulation and in vitro release evaluation of cefpodoxime using hydroxypropyl methylcellulose: a technical note. AAPS PharmSciTech. 2006;7(3):78.

    Article  PubMed  Google Scholar 

  22. Cirri M, Mura P, Rabasco AM, et al. Characterization of ibuproxam binary and ternary dispersions with hydrophilic carriers. Drug Dev Ind Pharm. 2004;30(1):65–74.

    Article  CAS  PubMed  Google Scholar 

  23. Mashru RC, Sutariya VB, Sankalia MG, Sankalia JM, Parikh PP. Development and evaluation of fast dissolving film of salbutamol sulphate. Drug Dev Ind Pharm. 2005;31:25–34.

    CAS  PubMed  Google Scholar 

  24. Ambike AA, Mahadik KR, Paradkar A. Stability study of amorphous valdecoxib. Int J Pharm. 2004;282:151–62.

    Article  CAS  PubMed  Google Scholar 

  25. Heo MY, Piao ZZ, Kim TW, Cao QR, Kim A, Lee BJ. Effect of solubilizing and microemulsifying excipients in polyethylene glycol 6000 solid dispersion on enhanced dissolution and bioavailability of ketoconazole. Arch Pharm Res. 2005;28(5):604–11.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

This research was supported by Department of Pharmacy, Faculty of medicine, University of Malaya by providing the facilities and requirements of research. I wish to thank all people that help during this project especially Prof. Kadhum A.H., Asst. Prof. Javary H.A., and Asst. Prof. Abdulla M.A.

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Authors and Affiliations

  1. Department of Pharmaceutics, College of Pharmacy, Baghdad University, Baghdad, Iraq

    Mowafaq M. Ghareeb, Alaa A. Abdulrasool & Ahmed A. Hussein

  2. Department of Pharmacy, Faculty of Medicine, Malaya University, Kuala Lumpur, Malaysia

    Mohammed I. Noordin

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  1. Mowafaq M. Ghareeb
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  2. Alaa A. Abdulrasool
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  3. Ahmed A. Hussein
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  4. Mohammed I. Noordin
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Correspondence to Mowafaq M. Ghareeb.

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Ghareeb, M.M., Abdulrasool, A.A., Hussein, A.A. et al. Kneading Technique for Preparation of Binary Solid Dispersion of Meloxicam with Poloxamer 188. AAPS PharmSciTech 10, 1206–1215 (2009). https://doi.org/10.1208/s12249-009-9316-0

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