Development and Evaluation of Poorly Water-Soluble Celecoxib as Solid Dispersions Containing Nonionic Surfactants Using Fluidized-Bed Granulation

• Main Authors: Hyeok Jin Kwon (Author), Eun-Ji Heo (Author), Young-Hwan Kim (Author), Sarah Kim (Author), Young-Ha Hwang (Author), Ji-Mi Byun (Author), Se Hyeop Cheon (Author), Sang Yeob Park (Author), Dong Yun Kim (Author), Kwan Hyung Cho (Author), Han-Joo Maeng (Author), Dong-Jin Jang (Author)
• Format: Book
• Published: MDPI AG, 2019-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1999-4923; 10.3390/pharmaceutics11030136
• Keywords: celecoxib; solid dispersion; nonionic surfactants; Cremophor RH40; fluid-bed granulation; tableting; pharmacokinetics; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 11, Iss 3, p 136 (2019)

The purpose of this study is to develop a solid dispersion system with improved dissolution, absorption, and patient compliance of poorly water-soluble celecoxib (CXB). Instead of sodium lauryl sulfate (SLS), an anionic surfactant used in the marketed product (Celebrex^&#174;), solubilization was performed using non-ionic surfactants with low toxicity. Cremophor RH40 (Cre-RH) was selected as the optimal solubilizer. Granules and tablets containing CXB and Cre-RH were prepared via fluid-bed and tableting processes, respectively. The morphology, crystallinity, flowability, dissolution, and pharmacokinetics for CXB-solid dispersion granules (SDGs) and the hardness and friability for CXB-solid dispersion tablets (SDTs) were evaluated. The solubility of CXB was found to be increased by about 717-fold when using Cre-RH. The dissolution of granules containing Cre-RH was found to be increased greatly compared with CXB API and Celebrex^&#174; (66.9% versus 2.3% and 37.2% at 120 min). The improvement of the dissolution was confirmed to be the same as that of granules in tablets. The CXB formulation resulted in 4.6- and 4.9-fold higher AUC_inf and <i>C</i>_max of CXB compared with those of an oral dose of CXB powder in rats. In short, these data suggest that the solid dispersion based on Cre-RH&#8212;a non-toxic solubilizer, non-ionic surfactant&#8212; may be an effective formulation for CXB to enhance its oral bioavailability and safety.