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AAPS PharmSciTech

, Volume 15, Issue 6, pp 1516–1526 | Cite as

A Method to Evaluate the Effect of Contact with Excipients on the Surface Crystallization of Amorphous Drugs

  • Si-Wei Zhang
  • Lian Yu
  • Jun Huang
  • Munir A. Hussain
  • Lotfi Derdour
  • Feng Qian
  • Melgardt M. de Villiers
Research Article

Abstract

Amorphous drugs are used to improve the solubility, dissolution, and bioavailability of drugs. However, these metastable forms of drugs can transform into more stable, less soluble, crystalline counterparts. This study reports a method for evaluating the effect of commonly used excipients on the surface crystallization of amorphous drugs and its application to two model amorphous compounds, nifedipine and indomethacin. In this method, amorphous samples of the drugs were covered by excipients and stored in controlled environments. An inverted light microscope was used to measure in real time the rates of surface crystal nucleation and growth. For nifedipine, vacuum-dried microcrystalline cellulose and lactose monohydrate increased the nucleation rate of the β polymorph from two to five times when samples were stored in a desiccator, while d-mannitol and magnesium stearate increased the nucleation rate 50 times. At 50% relative humidity, the nucleation rates were further increased, suggesting that moisture played an important role in the crystallization caused by the excipients. The effect of excipients on the crystal growth rate was not significant, suggesting that contact with excipients influences the physical stability of amorphous nifedipine mainly through the effect on crystal nucleation. This effect seems to be drug specific because for two polymorphs of indomethacin, no significant change in the nucleation rate was observed under the excipients.

KEY WORDS

amorphous drugs growth rate nucleation rate tablet excipients 

Notes

Acknowledgments

We thank Bristol-Myers Squibb Co. for supporting this work.

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Copyright information

© American Association of Pharmaceutical Scientists 2014

Authors and Affiliations

  • Si-Wei Zhang
    • 1
  • Lian Yu
    • 1
    • 2
  • Jun Huang
    • 3
  • Munir A. Hussain
    • 3
  • Lotfi Derdour
    • 3
  • Feng Qian
    • 4
  • Melgardt M. de Villiers
    • 1
  1. 1.School of PharmacyUniversity of Wisconsin-MadisonMadisonUSA
  2. 2.Department of ChemistryUniversity of Wisconsin-MadisonMadisonUSA
  3. 3.Bristol-Myers Squibb CompanyNew BrunswickUSA
  4. 4.School of MedicineTsinghua UniversityBeijingChina

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