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.
Highlights
Celecoxib (CXB) is a cyclooxygenase-2 selective and non-steroidal anti-inflammatory drug for osteoarthritis and rheumatoid arthritis [1,2]
It is known that CXB, a type II drug in biopharmaceutical classification system (BCS), is very poor in dissolution and oral absorption due to low solubility (3.2 μg/mL in water), in spite of its own therapeutic effect [3,4]
Celecoxib used in high-dose administration (i.e., 200–400 mg twice daily) requires improvement for oral absorption and biocompatibility through novel dosage form, and it would help to improve greatly patient compliance [11]
Summary
Celecoxib (CXB) is a cyclooxygenase-2 selective and non-steroidal anti-inflammatory drug for osteoarthritis and rheumatoid arthritis [1,2]. Celecoxib used in high-dose administration (i.e., 200–400 mg twice daily) requires improvement for oral absorption and biocompatibility through novel dosage form, and it would help to improve greatly patient compliance [11]. To overcome these issues of CXB, various strategies such as self-emulsifying drug delivery system [3], solid dispersion [4], lipid carrier [12], and dry elixir [13] have been reported. If there are ways to expect the effective solubilization of poorly water-soluble CXB without the use of additional substances, it might be one of the useful approaches
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