Article

Polymer incorporation method affects the physical stability of amorphous indomethacin in aqueous suspension

European Journal of Pharmaceutics and Biopharmaceutics, Elsevier, ISSN 1873-3441

Volume 96, 2015

DOI:10.1016/j.ejpb.2015.06.005, Dimensions: pub.1002628394, PMID: 26092472,

Authors

Surwase, S.A. (1) (2)
Itkonen, L. (1) (2)
Rades, T. (3)

* Corresponding author

Affiliations

Organisations

  1. (1) University of Helsinki, grid.7737.4
  2. (2) University of Otago, grid.29980.3a
  3. (3) University of Copenhagen, grid.5254.6, KU

Description

This study reports the potential of different polymers and polymer incorporation methods to inhibit crystallisation and maintain supersaturation of amorphous indomethacin (IND) in aqueous suspensions during storage. Three different polymers (poly(vinyl pyrrolidone) (PVP), hydroxypropyl methylcellulose (HPMC) and Soluplus® (SP)) were used and included in the suspensions either as a solid dispersion (SD) with IND or dissolved in the suspension medium prior to the addition of amorphous IND. The total concentrations of both IND and the polymer in the suspensions were kept the same for both methods of polymer incorporation. All the polymers (with both incorporation methods) inhibited crystallisation of the amorphous IND. The SDs were better than the predissolved polymer solutions at inhibiting crystallisation. The SDs were also better at maintaining drug supersaturation. SP showed a higher IND crystallisation inhibition and supersaturation potential than the other polymers. However, this depended on the method of addition. IND in SD with SP did not crystallise, nor did the SD generate any drug supersaturation, whereas IND in the corresponding predissolved SP solution crystallised (into the recently characterised η polymorphic form of the drug) but also led to a more than 20-fold higher IND solution concentration than that observed for crystalline IND. The ranking of the polymers with respect to crystallisation inhibition potential in SDs was SP≫PVP>HPMC. Overall, this study showed that both polymer type and polymer incorporation method strongly impact amorphous form stability and drug supersaturation in aqueous suspensions.

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University of Copenhagen

Danish Open Access Indicator

2015: Unused

Research area: Medicine

Danish Bibliometrics Indicator

2015: Level 2

Research area: Medicine

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Times Cited: 25

Field Citation Ratio (FCR): 6.35

Relative Citation ratio (RCR): 2.13