Sang-Min Cho

Pharmacokinetics and Anti-Gastric Ulceration Activity of Oral Administration of Aceclofenac and Esomeprazole in Rats

This study examined the effects of esomeprazole on aceclofenac pharmacokinetics and gastrointestinal complications in rats. Aceclofenac alone, or in combination with esomeprazole, was orally administered to male Sprague-Dawley rats. Plasma concentrations of aceclofenac, its major metabolite diclofenac, and esomeprazole were simultaneously determined by a novel liquid chromatography-tandem mass spectrometry method. Gastrointestinal damage was determined by measuring ulcer area and ulcer lesion index of the stomach. Oral administration of aceclofenac induced significant gastric ulceration, which was inhibited by esomeprazole administration. Following concurrent administration of aceclofenac and esomeprazole, overall pharmacokinetic profiles of aceclofenac and metabolic conversion to diclofenac were unaffected by esomeprazole. Aceclofenac metabolism and pharmacokinetics were not subject to significant food effects, whereas bioavailability of esomeprazole decreased in fed compared to fasting conditions. In contrast, the pharmacokinetics of aceclofenac and esomeprazole were significantly altered by different dosing vehicles. These results suggest that co-administration of esomeprazole with aceclofenac may reduce aceclofenac-induced gastrointestinal complications without significant pharmacokinetic interactions. The optimal combination and clinical significance of the benefits of the combination of aceclofenac and esomeprazole need to be further evaluated.

Spiral mouthpiece design in a dry powder inhaler to improve aerosolization

&NA; This study presents the effect of a spiral mouthpiece design in a carrier‐based dry powder inhalation on particle aerosol characteristics. Two kinds of mouthpieces, with spiral and non‐spiral shaped flow channels, were fabricated by 3D‐printing; particle image velocimetry and Anderson cascade impactor were performed to evaluate the drug aerosol characteristics. The obtained experimental results were in agreement with the simulation results of the computational fluid dynamics analysis. The spiral channel created a strong swirl motion of the air flow emitted from the mouthpiece exit, which produced angular momentum rather than the axial flow velocity in the forward direction. This is beneficial in terms of liberating the micronized drug particles from the carrier surface, and leads to more effective delivery of these drug particles to the peripheral target regions of the respiratory system. The spiral device could produce drug particles with significantly smaller mass median aerodynamic diameters and higher fine particle fraction than the non‐spiral device.

Evaluation of the effects of food on levodropropizine controlled-release tablet and its pharmacokinetic profile in comparison to that of immediate-release tablet

Background Levodropropizine is a non-opioid antitussive agent that inhibits cough reflex by reducing the release of sensory peptide in the peripheral region. To improve patients’ compliance, a controlled-release (CR) tablet is under development. The aim of this study was to compare the pharmacokinetic (PK) profiles of the CR and immediate-release (IR) tablets of levodropropizine. In addition, the effect of food on the PK properties of levodropropizine CR tablet in healthy subjects was evaluated. Subjects and methods A randomized, open-label, multiple-dose, three-treatment, three-period, six-sequence, crossover study was conducted on 47 healthy subjects. All subjects were randomly assigned to one of the six sequences, which involve combinations of the following three treatments: levodropropizine IR 60 mg three times in the fasted state (R), levodropropizine CR 90 mg two times in the fasted state (T), and levodropropizine CR 90 mg two times in the fed state (TF). Serial blood samples were collected up to 24 h after the first dose. Tolerability was assessed based on the vital signs, adverse events (AEs), and clinical laboratory tests. Results Levodropropizine CR showed lower maximum drug concentration (Cmax) and similar total exposure compared to levodropropizine IR. The geometric mean ratios (GMRs) (90% confidence intervals [CIs]) of T to R for the Cmax and area under the concentration–time curve from the 0 to 24 h time points (AUC0–24h) were 0.80 (0.75–0.85) and 0.89 (0.86–0.93), respectively. In the fed group, levodropropizine CR showed exposure similar to that in the fasted group. The GMRs (90% CIs) of TF to T for the Cmax and AUC0–24h were 0.90 (0.85–0.97) and 1.10 (1.05–1.14), respectively. No serious AEs occurred with both levodropropizine CR and IR tablets. Conclusion Total systemic exposure for levodropropizine was similar in subjects receiving the CR and IR formulations in terms of the AUC. Although food delayed the absorption of levodropropizine CR, systemic exposure was not affected.