Development and Evaluation of a Reconstitutable Dry Suspension to Improve the Dissolution and Oral Absorption of Poorly Water-Soluble Celecoxib

Abstract

This study aims at developing and evaluating reconstitutable dry suspension (RDS) improved for dissolution rate, oral absorption, and convenience of use of poorly water-soluble celecoxib (CXB). Micro-sized CXB particle was used to manufacture nanosuspension by using bead milling and then RDS was made by spray-drying the nanosuspension with effective resuspension agent, dextrin. The redispersibility, morphology, particle size, crystallinity, stability, dissolution, and pharmacokinetic profile of the RDS were evaluated. RDS was effectively reconstituted into nanoparticles in 775.8 ± 11.6 nm. It was confirmed that CXB particles are reduced into needle-shape ones in size after the bead-milling process, and the description of CXB was the same in the reconstituted suspension. Through the CXB crystallinity study using differential scanning calorimetry (DSC) and XRD analysis, it was identified that CXB has the CXB active pharmaceutical ingredient (API)’s original crystallinity after the bead milling and spray-drying process. In vitro dissolution of RDS was higher than that of CXB powder (93% versus 28% dissolution at 30 min). Furthermore, RDS formulation resulted in 5.7 and 6.3-fold higher area under the curve (AUC∞) and peak concentration (Cmax) of CXB compared to after oral administration of CXB powder in rats. Collectively, our results suggest that the RDS may be a potential oral dosage formulation for CXB to improve its bioavailability and patient compliance.

Isoliquiritigenin Nanosuspension Enhances Cytostatic Effects in A549 Lung Cancer Cells

“…Generally, a combination of polymer and surfactants are used to protect drug particles against aggregation via steric and electrosteric stabilization. However, excessive use of surfactants can lead to side effects such as promoting Ostwald ripening [22] and causing skin irritation and mucosal irritation [23]. Only a few studies have focused on the preparation of nanosuspensions with a single polymer stabilizer to avoid the aggregation of particles and improve the solubility of the insoluble drugs.…”

Employment of Alginate Floating In Situ Gel for Controlled Delivery of Celecoxib: Solubilization and Formulation Studies

“…The literature reported various solubilizing techniques to improve the solubility and oral absorption of CXB, such as a self-emulsifying system [4], mesoporous silica [5], nanosuspension [6,7], elixir [8], and solid dispersion [9]. Nevertheless, in previous studies, no attempt has been taken to investigate the aqueous solubility enhancement of CXB by the cosolvency approach.…”

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

“…Again, the use of non-ionic surfactants, which have advantages over ionic surfactants in terms of toxicity, mucosal compatibility, and biodegradability, may be considered [20,24]. In addition, the development of improved dosage formulations of CXB, a high-dose drug (generally 200–400 mg twice daily), will be able to improve oral bioavailability and thus reduce toxicity and enhance patient compliance [25]. Various formulations of CXB, such as a self-emulsifying system [26], mesoporous silica [27], nanosuspension [25,28], elixir [29], and solid dispersion [30,31] have been developed with respect to the issues of disadvantage and inconvenience.…”