Pharmaceutical Research

, Volume 33, Issue 3, pp 739–750 | Cite as

Dissolution Performance of High Drug Loading Celecoxib Amorphous Solid Dispersions Formulated with Polymer Combinations

  • Tian Xie
  • Lynne S. TaylorEmail author
Research Paper



The aims of this study were twofold. First, to evaluate the effectiveness of selected polymers in inhibiting solution crystallization of celecoxib. Second, to compare the release rate and crystallization tendency of celecoxib amorphous solid dispersions (ASDs) formulated with a single polymer, or binary polymer combinations.


The effectiveness of polymers, polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose (HPMC) or HPMC acetate succinate (HPMCAS), in maintaining supersaturation of celecoxib solutions was evaluated by performing nucleation induction time measurements. Crystallization kinetics of ASD suspensions were monitored using Raman spectroscopy. Dissolution experiments were carried out under non-sink conditions.


Pure amorphous celecoxib crystallized rapidly through both matrix and solution pathways. Matrix and solution crystallization was inhibited when celecoxib was molecularly mixed with a polymer, resulting in release of the drug to form supersaturated solutions. Cellulosic polymers were more effective than PVP in maintaining supersaturation. Combining a cellulosic polymer and PVP enabled improved drug release and stability to crystallization.


Inclusion of an effective solution crystallization inhibitor as a minor component in ternary dispersions resulted in prolonged supersaturation following dissolution. This study shows the feasibility of formulation strategies for ASDs where a major polymer component is used to achieve one key property e.g. release, while a minor polymer component is added to prevent crystallization.


amorphous solid dispersion crystallization dissolution supersaturation 



Amorphous solid dispersion




High performance liquid chromatography


Hydroxypropylmethyl cellulose


Hydroxypropylmethyl cellulose acetate succinate


Polyvinyl pyrrolidone


Sodium phosphate buffer





The Dane O. Kildsig Center for Pharmaceutical Processing Research is acknowledged for providing funding for this project.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Industrial and Physical Pharmacy, College of PharmacyPurdue UniversityWest LafayetteUSA

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