Preparation, characterization, and evaluation of celecoxib eutectic mixtures with adipic acid/saccharin for improvement of wettability and dissolution rate

Sang Min Hyun, Benjamin Joon Lee, Sharif Md Abuzar, Soohun Lee, Yechan Joo, Seung Hyeon Hong, Han Kang, Kyung Ae Kwon, Sitaram Velaga, Sung Joo Hwang

Research output: Contribution to journalArticle

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Abstract

Celecoxib (CEL) is a selective cyclooxygenase-2 (COX-2) inhibitor therapeutically indicated for the treatment of rheumatoid arthritis, osteoarthritis, acute pain, and inflammation. However, its poor solubility and dissolution rate significantly hinders its broader application. In this study, eutectic mixtures, as binary pharmaceutical compositions of CEL with adipic acid (ADI) and saccharin (SAC), were identified through a phase diagram and Tammann's triangle intended to improve the wettability and dissolution rate of poorly water-soluble CEL. The contact angles at 0s in the liquid-solid interface were approximately θs (theta) 79.7 ± 0.50° and 86.65 ± 0.45° for CEL-ADI and CEL-SAC, respectively, which were much lower than the value obtained for CEL (92.05 ± 0.75° θ). Moreover, a comparison of the disk intrinsic dissolution rate and powder dissolution properties demonstrated that eutectic mixtures significantly increased the dissolution rate compared with CEL and physical mixtures. A general relationship was elucidated and indicated that the dissolution rate was increased as the contact angle decreased (correlation coefficient, r = 0.9966 ± 0.0031). Therefore, CEL-ADI and CEL-SAC eutectics may offer a novel formulation strategy to enhance the solubility and oral bioavailability of CEL.

Original languageEnglish
Pages (from-to)61-71
Number of pages11
JournalInternational Journal of Pharmaceutics
Volume554
DOIs
Publication statusPublished - 2019 Jan 10

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Celecoxib
Wettability
Saccharin
Solubility
adipic acid
Cyclooxygenase 2 Inhibitors

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Hyun, Sang Min ; Lee, Benjamin Joon ; Abuzar, Sharif Md ; Lee, Soohun ; Joo, Yechan ; Hong, Seung Hyeon ; Kang, Han ; Kwon, Kyung Ae ; Velaga, Sitaram ; Hwang, Sung Joo. / Preparation, characterization, and evaluation of celecoxib eutectic mixtures with adipic acid/saccharin for improvement of wettability and dissolution rate. In: International Journal of Pharmaceutics. 2019 ; Vol. 554. pp. 61-71.
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abstract = "Celecoxib (CEL) is a selective cyclooxygenase-2 (COX-2) inhibitor therapeutically indicated for the treatment of rheumatoid arthritis, osteoarthritis, acute pain, and inflammation. However, its poor solubility and dissolution rate significantly hinders its broader application. In this study, eutectic mixtures, as binary pharmaceutical compositions of CEL with adipic acid (ADI) and saccharin (SAC), were identified through a phase diagram and Tammann's triangle intended to improve the wettability and dissolution rate of poorly water-soluble CEL. The contact angles at 0s in the liquid-solid interface were approximately θs (theta) 79.7 ± 0.50° and 86.65 ± 0.45° for CEL-ADI and CEL-SAC, respectively, which were much lower than the value obtained for CEL (92.05 ± 0.75° θ). Moreover, a comparison of the disk intrinsic dissolution rate and powder dissolution properties demonstrated that eutectic mixtures significantly increased the dissolution rate compared with CEL and physical mixtures. A general relationship was elucidated and indicated that the dissolution rate was increased as the contact angle decreased (correlation coefficient, r = 0.9966 ± 0.0031). Therefore, CEL-ADI and CEL-SAC eutectics may offer a novel formulation strategy to enhance the solubility and oral bioavailability of CEL.",
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Preparation, characterization, and evaluation of celecoxib eutectic mixtures with adipic acid/saccharin for improvement of wettability and dissolution rate. / Hyun, Sang Min; Lee, Benjamin Joon; Abuzar, Sharif Md; Lee, Soohun; Joo, Yechan; Hong, Seung Hyeon; Kang, Han; Kwon, Kyung Ae; Velaga, Sitaram; Hwang, Sung Joo.

In: International Journal of Pharmaceutics, Vol. 554, 10.01.2019, p. 61-71.

Research output: Contribution to journalArticle

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AU - Hyun, Sang Min

AU - Lee, Benjamin Joon

AU - Abuzar, Sharif Md

AU - Lee, Soohun

AU - Joo, Yechan

AU - Hong, Seung Hyeon

AU - Kang, Han

AU - Kwon, Kyung Ae

AU - Velaga, Sitaram

AU - Hwang, Sung Joo

PY - 2019/1/10

Y1 - 2019/1/10

N2 - Celecoxib (CEL) is a selective cyclooxygenase-2 (COX-2) inhibitor therapeutically indicated for the treatment of rheumatoid arthritis, osteoarthritis, acute pain, and inflammation. However, its poor solubility and dissolution rate significantly hinders its broader application. In this study, eutectic mixtures, as binary pharmaceutical compositions of CEL with adipic acid (ADI) and saccharin (SAC), were identified through a phase diagram and Tammann's triangle intended to improve the wettability and dissolution rate of poorly water-soluble CEL. The contact angles at 0s in the liquid-solid interface were approximately θs (theta) 79.7 ± 0.50° and 86.65 ± 0.45° for CEL-ADI and CEL-SAC, respectively, which were much lower than the value obtained for CEL (92.05 ± 0.75° θ). Moreover, a comparison of the disk intrinsic dissolution rate and powder dissolution properties demonstrated that eutectic mixtures significantly increased the dissolution rate compared with CEL and physical mixtures. A general relationship was elucidated and indicated that the dissolution rate was increased as the contact angle decreased (correlation coefficient, r = 0.9966 ± 0.0031). Therefore, CEL-ADI and CEL-SAC eutectics may offer a novel formulation strategy to enhance the solubility and oral bioavailability of CEL.

AB - Celecoxib (CEL) is a selective cyclooxygenase-2 (COX-2) inhibitor therapeutically indicated for the treatment of rheumatoid arthritis, osteoarthritis, acute pain, and inflammation. However, its poor solubility and dissolution rate significantly hinders its broader application. In this study, eutectic mixtures, as binary pharmaceutical compositions of CEL with adipic acid (ADI) and saccharin (SAC), were identified through a phase diagram and Tammann's triangle intended to improve the wettability and dissolution rate of poorly water-soluble CEL. The contact angles at 0s in the liquid-solid interface were approximately θs (theta) 79.7 ± 0.50° and 86.65 ± 0.45° for CEL-ADI and CEL-SAC, respectively, which were much lower than the value obtained for CEL (92.05 ± 0.75° θ). Moreover, a comparison of the disk intrinsic dissolution rate and powder dissolution properties demonstrated that eutectic mixtures significantly increased the dissolution rate compared with CEL and physical mixtures. A general relationship was elucidated and indicated that the dissolution rate was increased as the contact angle decreased (correlation coefficient, r = 0.9966 ± 0.0031). Therefore, CEL-ADI and CEL-SAC eutectics may offer a novel formulation strategy to enhance the solubility and oral bioavailability of CEL.

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