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 (C_max) 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.

Sorafenib, an oral multikinase inhibitor, exhibits a highly variable absorption profile due to enterohepatic reabsorption and poor solubility. SYO-1644 improved the solubility of sorafenib by nanoparticulation technology leading to enhanced bioavailability. To evaluate the pharmacokinetically equivalent dose of SYO-1644 to the reference Nexavar^® 200 mg, a randomized, open-label, replicated two-period study was conducted in healthy volunteers. A total of 32 subjects orally received a single dose of the following assigned treatment under a fasted state in the first period and repeated once more in the second period with a two-week washout: SYO-1644 100, 150 and 200 mg and Nexavar^® 200 mg. Pharmacokinetic (PK) samples were collected up to 168 h post-dose. The PK profile was evaluated by both non-compartmental analysis and population PK method. With the final model, 2 × 2 crossover trial scenarios with Nexavar^® 200 mg and each dose of SYO-1644 ranging from 100 to 150 mg were repeated 500 times by Monte Carlo simulation, and the proportion of bioequivalence achievement was assessed. Transit absorption compartments, followed by a one-compartment model with first-order elimination and enterohepatic reabsorption components were selected as the final model. The simulation results demonstrated that the SYO-1644 dose between 120 and 125 mg could yielded the highest proportion of bioequivalence.

Objectives: This study explores the development and evaluation of a bilayer sustained-release (SR) tablet formulation of ruxolitinib. As a BCS Class 1 drug, ruxolitinib requires twice-daily dosing due to its short half-life. We designed a bilayer tablet that integrates immediate-release (IR) and SR components in varying ratios to achieve sustained plasma concentrations, which we evaluated using discriminative analysis. Methods: Bilayer tablets combining IR and SR components were prepared in different ratios. In vitro dissolution tests and pharmacokinetic studies were conducted using Beagle dogs, followed by the evaluation of in vivo–in vitro correlation (IVIVC), along with a discriminative pharmacokinetic analysis focused on the SR layer. Results: A discriminative pharmacokinetic and IVIVC analysis was applied to all bilayer tablets, offering clearer insights into the plasma concentration and dissolution profiles. Pharmacokinetic studies showed that test formulation F4, which has a 20:20 IR-to-SR ratio, is expected to provide a similar area under the curve (AUC) while prolonging exposure compared to the reference IR tablet. Conclusions: This study highlights the potential of a bilayer tablet approach, combined with discriminative pharmacokinetic and IVIVC analysis, for creating a sustained-release dosage form of ruxolitinib.