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Comparison Between Hot-Melt Extrusion and Spray-Drying for Manufacturing Solid Dispersions of the Graft Copolymer of Ethylene Glycol and Vinylalcohol

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ABSTRACT

Purpose

To investigate the effect of the manufacturing method (spray-drying or hot-melt extrusion) on the kinetic miscibility of miconazole and the graft copolymer poly(ethyleneglycol-g-vinylalcohol). The effect of heat pre-treatment of solutions used for spray-drying and the use of spray-dried copolymer as excipient for hot-melt extrusion was investigated.

Method

The solid dispersions were prepared at different drug-polymer ratios and analyzed with modulated differential scanning calorimetry and X-ray powder diffraction.

Results

Miconazole either mixed with the PEG-fraction of the copolymer or crystallized in the same or a different polymorph as the starting material. The kinetic miscibility was higher for the solid dispersions obtained from solutions which were pre-heated compared to those spray-dried from solutions at ambient temperature. Hot-melt extrusion resulted in an even higher mixing capability. Here the use of the spray-dried copolymer did not show any benefit concerning the kinetic miscibility of the drug and copolymer, but it resulted in a remarkable decrease in the torque experienced by the extruder allowing extrusion at lower temperature and torque.

Conclusion

The manufacturing method has an influence on the mixing capacity and phase behavior of solid dispersions. Heat pre-treatment of the solutions before spray-drying can result in a higher kinetic miscibility. Amorphization of the copolymer by spray-drying before using it as an excipient for hot-melt extrusion can be a manufacturing benefit.

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REFERENCES

  1. Janssens S, Van den Mooter G. Review: physical chemistry of solid dispersions. J Pharm Pharmacol. 2009;61:1571–86.

    CAS  PubMed  Google Scholar 

  2. Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2000;50:47–60.

    CAS  PubMed  Google Scholar 

  3. Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today. 2007;12:1068–75.

    CAS  PubMed  Google Scholar 

  4. Janssens S, Denivelle S, Rombaut P, Van den Mooter G. Influence of polyethylene glycol chain length on compatibility and release characteristics of ternary solid dispersions of itraconazole in polyethylene glycol/hydroxypropylmethylcellulose 2910 E5 blends. Eur J Pharm Sci. 2008;35(3):203–2010.

    CAS  PubMed  Google Scholar 

  5. Janssens S, de Armas HN, Roberts CJ, Van den Mooter G. Characterization of ternary solid dispersions of itraconazole, PEG 6000 and HPMC 2910 E5. J Pharm Sci. 2008;97(6):2110–20.

    CAS  PubMed  Google Scholar 

  6. Six K, Verreck G, Peeters J, Brewster M, Van den Mooter G. Increased physical stability and improved dissolution properties of itraconazole, a class II drug, by solid dispersions that combine fast-and slow dissolving polymers. J Pharm Sci. 2004;93(1):124–31.

    CAS  PubMed  Google Scholar 

  7. Janssens S, Novoa de Armas H, Remon JP, Van den Mooter G. The use of a new hydrophilic polymer, Kollicoat IR®, in the formulation of solid dispersions of itraconazole. Eur J Pharm Sci. 2007;30:288–94.

    CAS  PubMed  Google Scholar 

  8. Janssens S, Anné M, Rombaut P, Van den Mooter G. Spray-drying from complex solvent systems broadens the applicability of Kollicoat IR as a carrier in the formulation of solid dispersions. Eur J Pharm Sci. 2009;37:241–8.

    CAS  PubMed  Google Scholar 

  9. Guns S, Kayaert P, Martens JA, Van Humbeeck J, Mathot V, Pijpers T, et al. Characterization of the copolymer poly(ethyleneglycol-g-vinylalcohol) as a potential carrier in the formulation of solid dispersions. Eur J Pharm Biopharm. 2010;74(2):239–47.

    CAS  PubMed  Google Scholar 

  10. Six K, Verreck G, Peeters J, Augustijns P, Kinget R, Van den Mooter G. Characterization of glassy itraconazole: a comparative study of its molecular mobility below T(g) with that of structural analogues using MTDSC. Int J Pharm. 2001;213:163–73.

    CAS  PubMed  Google Scholar 

  11. Yu L. Inferring thermodynamic stability relationship of polymorphs from melting data. J Pharm Sci. 1995;84:966–74.

    CAS  PubMed  Google Scholar 

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ACKNOWLEDGMENTS

SG and PK acknowledge the Agency for Innovation by Science and Technology in Flanders (IWT) for a Ph.D grant. The authors acknowledge financial support from FWO-Vlaanderen.

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Authors and Affiliations

  1. Laboratory for Pharmacotechnology and Biopharmacy, Catholic University of Leuven, Gasthuisberg O&N2, Herestraat 49, Box 921, 3000, Leuven, Belgium

    Sandra Guns, Aswin Dereymaker, Pieterjan Kayaert & Guy Van den Mooter

  2. SciTe B.V., Ridder Vosstraat 6, 6162 AX, Geleen, the Netherlands

    Vincent Mathot

  3. Department of Chemistry, Catholic University of Leuven, Celestijnenlaan 200f, box 2404, 3001, Heverlee, Belgium

    Vincent Mathot

  4. Centre for Surface Chemistry and Catalysis, Catholic University of Leuven, Kasteelpark Arenberg 23, 3001, Heverlee, Belgium

    Johan A. Martens

Authors
  1. Sandra Guns
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  2. Aswin Dereymaker
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  3. Pieterjan Kayaert
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  4. Vincent Mathot
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  5. Johan A. Martens
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  6. Guy Van den Mooter
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Corresponding author

Correspondence to Guy Van den Mooter.

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Guns, S., Dereymaker, A., Kayaert, P. et al. Comparison Between Hot-Melt Extrusion and Spray-Drying for Manufacturing Solid Dispersions of the Graft Copolymer of Ethylene Glycol and Vinylalcohol. Pharm Res 28, 673–682 (2011). https://doi.org/10.1007/s11095-010-0324-2

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  • DOI: https://doi.org/10.1007/s11095-010-0324-2

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