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

Abstract

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®), 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® (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 AUCinf and Cmax 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—a non-toxic solubilizer, non-ionic surfactant— may be an effective formulation for CXB to enhance its oral bioavailability and safety.

Effect of Micronization on Panax notoginseng: In Vitro Dissolution and In Vivo Bioavailability Evaluations

“…The effects of particle size and hydrothermal treatment (Powder 4 was treated at 30, 40, 50, and 100°C) on the dissolution behavior of the PNP were investigated. Dissolution studies were carried out on a dissolution apparatus (ZRS-8L, Tianda Tianfa, China) with a rotation speed of 75 rpm according to the China Pharmacopoeia apparatus III paddle method [ 32 , 33 ]. The tests were performed in 150 mL of freshly prepared aqueous solution and simulated gastric fluid (10 g/L pepsin, 0.1 M HCL, pH = 1.2, ChP 2015).…”

Effect of micronization on Panax notoginseng: In vitro dissolution & in vivo bioavailability evaluations

“…The effects of particle size and hydrothermal treatment (Powder 4 were treated at 30, 40, 50, and 100°C) on the dissolution behavior of the PNP were investigated. Dissolution studies were carried out on a dissolution apparatus (ZRS-8L, Tianda Tianfa, China) with a rotation speed of 75 rpm according to the China Pharmacopoeia apparatus paddle method [24,25] The content of notoginsenoside R 1 and ginsenosides Rg 1 and Rb 1 in the medium were determined by HPLC as described above. Because the dissolution of ingredients was affected by the particle size, the dissolution rate calculated using the revised equation is as follow:…”

Preparation and Evaluation of Eudragit L100-PEG Proliponiosomes for Enhanced Oral Delivery of Celecoxib

“…To address this issue, Celebrex, a commercially available CXB product, contains sodium dodecyl sulfate (SDS) as a solubilizer. Although this anionic surfactant is well-known for its high drug solubilizing potential with the characteristic micelle-forming property [5], several toxicity concerns have always been disputed, such as skin and mucosal irritations [6]. Thus, various formulation approaches have been made to improve the solubility and dissolution rate of CXB without using anionic surfactants.…”

“…Thus, various formulation approaches have been made to improve the solubility and dissolution rate of CXB without using anionic surfactants. These strategies can be categorized into mainly two types: amorphization [6][7][8] and nanonization [9][10][11].…”