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

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Abbreviations

ASD:

Amorphous solid dispersion

CEX:

Celecoxib

HPLC:

High performance liquid chromatography

HPMC:

Hydroxypropylmethyl cellulose

HPMCAS:

Hydroxypropylmethyl cellulose acetate succinate

PVP:

Polyvinyl pyrrolidone

SPB:

Sodium phosphate buffer

UV:

Ultraviolet

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ACKNOWLEDGMENTS AND DISCLOSURES

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

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Authors and Affiliations

  1. Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA

    Tian Xie & Lynne S. Taylor

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  1. Tian Xie
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  2. Lynne S. Taylor
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Correspondence to Lynne S. Taylor.

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Xie, T., Taylor, L.S. Dissolution Performance of High Drug Loading Celecoxib Amorphous Solid Dispersions Formulated with Polymer Combinations. Pharm Res 33, 739–750 (2016). https://doi.org/10.1007/s11095-015-1823-y

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  • DOI: https://doi.org/10.1007/s11095-015-1823-y

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