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Ability of Different Polymers to Inhibit the Crystallization of Amorphous Felodipine in the Presence of Moisture

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Abstract

Purpose

To investigate the ability of various polymers to inhibit the crystallization of amorphous felodipine from amorphous molecular dispersions in the presence of absorbed moisture.

Methods

Spin coated films of felodipine with poly(vinylpyrrolidone) (PVP), hydroxypropylmethylcellulose acetate succinate (HPMCAS) and hydroxypropylmethylcellulose (HPMC) were exposed to different storage relative humidities and nucleation rates were measured using polarized light microscopy. Solid dispersions were further characterized using differential scanning calorimetry, infrared spectroscopy and gravimetric measurement of water vapor sorption.

Results

It was found that the polymer additive reduced nucleation rates whereas absorbed water enhanced the nucleation rate as anticipated. When both polymer and water were present, nucleation rates were reduced relative to those of the pure amorphous drug stored at the same relative humidity, despite the fact that the polymer containing systems absorbed more water. Differences between the stabilizing abilities of the various polymers were observed and these were explained by the variations in the moisture contents of the solid dispersions caused by the different hygroscopicities of the component polymers. No correlations could be drawn between nucleation rates and the glass transition temperature (T g) of the system. PVP containing solid dispersions appeared to undergo molecular level changes on exposure to moisture which may be indicative of phase separation.

Conclusions

In conclusion, it was found that for a given storage relative humidity, although the addition of a polymer increases the moisture content of the system relative to that of the pure amorphous drug, the crystallization tendency was still reduced.

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References

  1. W. L. Chiou and S. Riegelman. Pharmaceutical applications of solid dispersion systems. J. Pharm. Sci. 60:1281–1302 (1971).

    Article  PubMed  CAS  Google Scholar 

  2. J. L. Ford. The current status of solid dispersions. Pharm. Acta Helv. 61:69–88 (1986).

    PubMed  CAS  Google Scholar 

  3. A. T. M. Serajuddin. Solid dispersions of poorly water-soluble drugs: early promises, subsequent problems and recent breakthroughs. J. Pharm. Sci. 88:1058–1066 (1999).

    Article  PubMed  CAS  Google Scholar 

  4. C. Leuner and J. Dressman. Improving drug solubility for oral delivery using solid dispersions. Eur. J. Pharm. Biopharm. 50:47–60 (2000).

    Article  PubMed  CAS  Google Scholar 

  5. M. Yoshioka, B. C. Hancock, and G. Zografi. Inhibition of indomethacin crystallization in poly(vinylpyrrolidone). J. Pharm. Sci. 84:983–986 (1995).

    Article  PubMed  CAS  Google Scholar 

  6. L. S. Taylor and G. Zografi. Spectroscopic characterization of interactions between PVP and indomethacin in amorphous molecular dispersions. Pharm. Res. 14:1691–1698 (1997).

    Article  PubMed  CAS  Google Scholar 

  7. T. Hino and J. L. Ford. Characterization of the hydroxypropylmethylcellulose–nicontinamide binary system. Int. J. Pharm. 219:39–49 (2001).

    Article  PubMed  CAS  Google Scholar 

  8. K. Yamashita, T. Nakate, K. Okimoto, A. Ohike, Y. Tokunaga, R. Ibuki, K. Higaki, and T. Kimura. Establishment of new preparation method for solid dispersion formulation of tacrolimus. Int. J. Pharm. 267:79–91 (2003).

    Article  PubMed  CAS  Google Scholar 

  9. T. Matsumoto and G. Zografi. Physical properties of solid dispersions of indomethacin with poly(vinylpyrrolidone) and poly(vinylpyrrolidone-co-vinyl acetate) in relation to indomethacin crystallization. Pharm. Res. 16:1722–1728 (1999).

    Article  PubMed  CAS  Google Scholar 

  10. T. Miyazaki, S. Yoshioka, Y. Aso, and S. Kojima. Ability of poly(vinylpyrrolidone) and polyacrylic acid to inhibit the crystallization of amorphous acetaminophen. J. Pharm. Sci. 93:2710–2717 (2004).

    Article  PubMed  CAS  Google Scholar 

  11. H. Konno and L. S. Taylor. Influence of different polymers on the crystallization tendency of molecularly dispersed amorphous felodipine. J. Pharm. Sci. 95:2692–2705 (2006).

    Article  PubMed  CAS  Google Scholar 

  12. G. Zografi. States of water associated with solids. Drug Dev. Ind. Pharm. 14:1905–1926 (1988).

    Article  CAS  Google Scholar 

  13. C. Ahlneck and G. Zografi. The molecular basis of moisture effects on the physical and chemical stability of drugs in the solid state. Int. J. Pharm. 62:87–95 (1990).

    Article  CAS  Google Scholar 

  14. S. L. Shamblin and G. Zografi. The effects of absorbed water on the properties of amorphous mixtures containing sucrose. Pharm. Res. 16:1119–1124 (1999).

    Article  PubMed  CAS  Google Scholar 

  15. C. A. Oksanen and G. Zografi. The relationship between the glass transition temperature and water vapor absorption by poly(vinylpyrrolidone). Pharm. Res. 7:654–657 (1990).

    Article  PubMed  CAS  Google Scholar 

  16. L. S. Taylor, F. W. Langkilde, and G. Zografi. Fourier transform Raman spectroscopic study of the interaction of water vapor with amorphous polymers. J. Pharm. Sci. 90:888–901 (2001).

    Article  PubMed  CAS  Google Scholar 

  17. V. Andronis and G. Zografi. Crystal nucleation and growth of indomethacin polymorphs from the amorphous state. J. Non-Cryst. Solids 271:236–248 (2000).

    Article  CAS  Google Scholar 

  18. S. Inoue and R. Oldenbourg. Microscopes. Handbook of Optics, Volume II, Bass, M. (ed), McGraw-Hill, New York, 1995.

  19. L. S. Taylor and G. Zografi. Sugar–polymer hydrogen bond interactions in lyophilized amorphous mixtures. J. Pharm. Sci. 87:1615–1621 (1998).

    Article  PubMed  CAS  Google Scholar 

  20. B. C. Hancock and G. Zografi. Characteristics and significance of amorphous state in pharmaceutical systems. J. Pharm. Sci. 86:1–12 (1997).

    Article  PubMed  CAS  Google Scholar 

  21. B. Makower and W. C. Dye. Equilibrium moisture content and crystallization of amorphous sucrose and glucose. J. Agric. Food Chem. 4:72–77 (1956).

    Article  CAS  Google Scholar 

  22. H. Imaizumi, N. Nambu and T. Nagai. Stability and several physical properties of amorphous and crystalline forms of indomethacin. Chem. Pharm. Bull. 28:2565–2569 (1980).

    PubMed  CAS  Google Scholar 

  23. C. Schimitt, C. W. Davis, and S. T. Long. Moisture-dependent crystallization of amorphous lamotrigine mesylate. J. Pharm. Sci. 85:1215–1219 (1996).

    Article  Google Scholar 

  24. V. Andronis, M. Yoshioka, and G. Zografi. Effects of sorbed water on the crystallization of indomethacin from the amorphous state. J. Pharm. Sci. 86:346–351 (1997).

    Article  PubMed  CAS  Google Scholar 

  25. F. Tanno, Y. Nishiyama, H. Kokubo and S. Obara. Evaluation of hypromellose acetate succinate (HPMCAS) as a carrier in solid dispersions. Drug Dev. Ind. Pharm. 30:9–17 (2004).

    Article  PubMed  CAS  Google Scholar 

  26. A. Saleki-Gerhard and G. Zografi. Non-isothermal and isothermal crystallization of amorphous state. Pharm. Res. 11:1166–1173 (1994).

    Article  Google Scholar 

  27. B. C. Hancock and G. Zografi. The relationship between glass transition temperature and water content of amorphous pharmaceutical solids. Pharm. Res. 11:471–477 (1994).

    Article  PubMed  CAS  Google Scholar 

  28. G. Van den Mooter, M. Wuyts, N. Blaton, R. Busson, P. Grobet, P. Augustijns, and R. Kinget. Physical stabi-lisation of amorphous ketoconazole in solid dispersions with polyvinylpyrrolidone K25. Eur. J. Pharm. Sci. 12:261–269 (2001).

    Article  PubMed  Google Scholar 

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Acknowledgements

Professor George Zografi is thanked for many enlightening discussions about this research. The authors are grateful to Dr. Sheri L. Shamblin for helpful comments. LST thanks AFPE/AACP for a New Investigator Award. HK acknowledges Astellas Pharma Inc. for granting him a leave of absence to undertake this work.

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Authors and Affiliations

  1. Department of Industrial and Physical Pharmacy, School of Pharmacy, Purdue University, West Lafayette, IN, 47907, USA

    Hajime Konno & Lynne S. Taylor

  2. Astellas Pharma Inc., 180 Ohzumi, Yaizu, Shizuoka, 425-0072, Japan

    Hajime Konno

Authors
  1. Hajime Konno
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  2. Lynne S. Taylor
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Correspondence to Lynne S. Taylor.

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Konno, H., Taylor, L.S. Ability of Different Polymers to Inhibit the Crystallization of Amorphous Felodipine in the Presence of Moisture. Pharm Res 25, 969–978 (2008). https://doi.org/10.1007/s11095-007-9331-3

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  • DOI: https://doi.org/10.1007/s11095-007-9331-3

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