Celecoxib Nanoformulations with Enhanced Solubility, Dissolution Rate, and Oral Bioavailability: Experimental Approaches over In Vitro/In Vivo Evaluation

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2023-02-01

Author

Arslan, Aslıhan
Yet, Barbaros
NEMUTLU, EMİRHAN
AKDAĞ ÇAYLI, YAĞMUR
EROĞLU, HAKAN
ÖNER, LEVENT

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Celecoxib (CXB) is a Biopharmaceutical Classification System (BCS) Class II molecule with high permeability that is practically insoluble in water. Because of the poor water solubility, there is a wide range of absorption and limited bioavailability following oral administration. These unfavorable properties can be improved using dry co-milling technology, which is an industrial applicable technology. The purpose of this study was to develop and optimize CXB nanoformulations prepared by dry co-milling technology, with a quality by design approach to maintain enhanced solubility, dissolution rate, and oral bioavailability. The resulting co-milled CXB composition using povidone (PVP), mannitol (MAN) and sodium lauryl sulfate (SLS) showed the maximum solubility and dissolution rate in physiologically relevant media. Potential risk factors were determined with an Ishikawa diagram, important risk factors were selected with Plackett-Burman experimental design, and CXB compositions were optimized with Central Composite design (CCD) and Bayesian optimization (BO). Physical characterization, intrinsic dissolution rate, solubility, and stability experiments were used to evaluate the optimized co-milled CXB compositions. Dissolution and permeability studies were carried out for the resulting CXB nanoformulation. Oral pharmacokinetic studies of the CXB nanoformulation and reference product were performed in rats. The results of in vitro and in vivo studies show that the CXB nanoformulations have enhanced solubility (over 4.8-fold (8.6 ± 1.06 µg/mL vs. 1.8 ± 0.33 µg/mL) in water when compared with celecoxib pure powder), and dissolution rate (at least 85% of celecoxib is dissolved in 20 min), and improved oral pharmacokinetic profile (the relative bioavailability was 145.2%, compared to that of Celebrex®, and faster tmax 3.80 ± 2.28 h vs. 6.00 ± 3.67 h, indicating a more rapid absorption rate).

Subject Keywords

Bayesian optimization, black-box, celecoxib, central composite design, characterization, dry co-milling, intrinsic dissolution rate, pharmacokinetics, response surface methodology

URI

https://hdl.handle.net/11511/102733

Journal

Pharmaceutics

DOI

https://doi.org/10.3390/pharmaceutics15020363

Collections

Graduate School of Informatics, Article

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Citation Formats

A. Arslan, B. Yet, E. NEMUTLU, Y. AKDAĞ ÇAYLI, H. EROĞLU, and L. ÖNER, “Celecoxib Nanoformulations with Enhanced Solubility, Dissolution Rate, and Oral Bioavailability: Experimental Approaches over In Vitro/In Vivo Evaluation,” Pharmaceutics, vol. 15, no. 2, pp. 0–0, 2023, Accessed: 00, 2023. [Online]. Available: https://hdl.handle.net/11511/102733.