Pharmaceutical Research

, 26:2599

Effects of Polymer Type and Storage Relative Humidity on the Kinetics of Felodipine Crystallization from Amorphous Solid Dispersions

  • Alfred C. F. Rumondor
  • Lindsay A. Stanford
  • Lynne S. Taylor
Research Paper

DOI: 10.1007/s11095-009-9974-3

Cite this article as:
Rumondor, A.C.F., Stanford, L.A. & Taylor, L.S. Pharm Res (2009) 26: 2599. doi:10.1007/s11095-009-9974-3

Abstract

Purpose

The objective of this study was to investigate the effects of polymer type and storage relative humidity (RH) on the crystallization kinetics of felodipine from amorphous solid dispersions.

Methods

Crystallization of the model drug felodipine from amorphous solid dispersion samples containing poly(vinyl pyrrolidone) (PVP) and hypromellose acetate succinate (HPMCAS) were evaluated. Samples at three different drug–polymer weight ratios (10, 25, and 50 wt. % polymer) were prepared and stored at six different RHs (0%, 32%, 52% or 66%, 75%, 86%, and 93%). Periodically, the fraction of the drug that had crystallized from the samples was quantified using powder X-ray diffractometry (PXRD).

Results

Felodipine crystallization rates from PVP-containing dispersions were found to be very sensitive to changes in storage RH, while crystallization rates from HPMCAS-containing dispersions were not. PVP and HPMCAS were similar in terms of their ability to inhibit crystallization at low RH, but when the storage RH was increased to 75% or above, felodipine crystallization from PVP-containing solid dispersions proceeded much faster. It is hypothesized that this trend was caused by moisture-induced drug–polymer immiscibility in PVP-felodipine system. For PVP-containing solid dispersion samples stored at 75% RH and above, crystallization of the model drug felodipine seemed to approach a kinetic plateau, whereby a fraction of the drug still remained amorphous even after storage for 500 days or more.

Conclusions

The physical stability of solid dispersions as a function of RH is highly dependent on the polymer used to form the solid dispersion, with PVP-containing dispersions being much less physically stable at high RH than HPMCAS-containing dispersions.

KEY WORDS

crystallization felodipine hygroscopicity powder X-ray diffractometry relative humidity 

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Alfred C. F. Rumondor
    • 1
    • 2
  • Lindsay A. Stanford
    • 1
  • Lynne S. Taylor
    • 1
  1. 1.Department of Industrial and Physical Pharmacy, School of PharmacyPurdue UniversityWest LafayetteUSA
  2. 2.Pharmaceutical and Analytical Research and DevelopmentAstraZeneca Pharmaceuticals LPWilmingtonUSA