Despite the various therapeutic benefits and high tolerance of orally administered silybin, poor water-solubility can be the main restrictive physicochemical feature, which results in low oral bioavailability in the absorption. A milk thistle nanocrystal formulation (HM40) was prepared using a modified wet-milling method. Comprehensive characterization was performed to determine the physical morphology, crystallinity, and physicochemical properties. The long-term stability was evaluated over 24 months. In vitro silybin release was assessed at pH 1.2 for 2 h, followed by pH 6.8 for 4 h. Finally, in vivo pharmacokinetic studies were conducted in rats and healthy human volunteers. HM40 exhibited a nanocrystal structure maintaining crystallinity and enhanced the solubility and dissolution of silybin compared to that of the raw material. The stability over 24 months revealed consistent surface morphology, particle size, silybin content, and solubility. In vitro release profiles indicated a significant increase in the silybin release from HM40. In vivo pharmacokinetic studies demonstrated that HM40 showed 2.61- and 1.51-fold higher oral bioavailability in rats and humans, respectively, than that of the reference capsule. HM40 formulation presents a stable and promising approach for the oral delivery of poorly water-soluble silybin, with the potential for use in pharmaceutical formulations containing milk thistle.

Camostat mesylate is expected to be promising as a treatment option for COVID-19, in addition to other indications for which it is currently used. Furthermore, in vitro experiments have confirmed the potential of camostat and its metabolites to be effective against COVID-19. Therefore, clinical trials were conducted to evaluate the safety and pharmacokinetic characteristics of camostat after single-dose administration. Additionally, we aim to predict the pharmacokinetics of repeated dosing through modeling and simulation based on clinical trials. Clinical trials were conducted on healthy Korean adults, and an analysis was carried out of the metabolites of camostat, GBPA, and GBA. Pharmacokinetic modeling and simulation were performed using Monolix. There were no safety issues (AEs, physical examinations, clinical laboratory tests, vital sign measurements, and ECG) during the clinical trial. The pharmacokinetic characteristics at various doses were identified. It was confirmed that AUC _last and C_max increased in proportion to dose in both GBPA and GBA, and linearity was also confirmed in log-transformed power model regression. Additionally, the accumulation index was predicted (1.12 and 1.08 for GBPA and GBA). The pharmacokinetics of camostat for various dose administrations and indications can be predicted prior to clinical trials using the developed camostat model. Furthermore, it can be used for various indications by connecting it with pharmacodynamic information.

Influenza A virus (IAV) is a major cause of respiratory infections worldwide. Current preventive measures, though effective for decades, face limitations due to the continuous evolution of viral strains and challenges in targeting specific viral proteins. In this study, we conducted in vivo screenings to evaluate the antiviral properties of various promising polymers to overcome the limitations of current virus infection prevention strategies. Subsequently, we performed detailed physiological and pathological assessments over an extended infection period. In the animal experiments regarding weight loss, a key symptom of viral infection, the group treated with xanthan gum (XG) showed significant suppression of weight loss compared to the untreated group starting from 3 DPI. Throughout the experiment, the treated group maintained a body weight similar to that of the uninfected group. In the virus titration and lung tissue pathology analysis, the group treated with the test substance showed a significantly lower viral load and tissue pathology results closer to normal compared to the untreated group. Additionally, we conducted in vitro combination treatment experiments to evaluate the antiviral ability of XG in conjunction with camostat, a previously known TMPRSS2 inhibitor. The results demonstrated that in the combination-treated groups, XG and camostat exhibited significantly higher cell viability at lower concentrations compared to the single-treatment groups for influenza A H1N1, A H3N2, and B type. These results indicate that XG possesses potential capabilities in inhibiting respiratory viruses and may be utilized in conjunction with existing antiviral treatments.

Donepezil patch was developed to replace the original oral formulation. To accurately describe the pharmacokinetics of donepezil and investigate compatible doses between two formulations, a population pharmacokinetic model for oral and transdermal patches was built based on a clinical study. Plasma donepezil levels were analyzed via liquid chromatography/tandem mass spectrometry. Non-compartmental analyses were performed to derive the initial parameters for compartmental analyses. Compartmental analysis (CA) was performed with NLME software NONMEM assisted by Perl-speaks-NONMEM, and R. Model evaluation was proceeded via visual predictive checks (VPC), goodness-of-fit (GOF) plotting, and bootstrap method. The bioequivalence test was based on a 2 × 2 crossover design, and parameters of AUC and C_max were considered. We found that a two-compartment model featuring two transit compartments accurately describes the pharmacokinetics of nine subjects administered in oral, as well as of the patch-dosed subjects. Through evaluation, the model was proven to be sufficiently accurate and suitable for further bioequivalence tests. Based on the bioequivalence test, 114 mg/101.3 cm²–146 mg/129.8 cm² of donepezil patch per week was equivalent to 10 mg PO donepezil per day. In conclusion, the pharmacokinetic model was successfully developed, and acceptable parameters were estimated. However, the size calculated by an equivalent dose of donepezil patch could be rather large. Further optimization in formulation needs to be performed to find appropriate usability in clinical situations.

The SARS‐CoV‐2 caused COVID‐19 pandemic has posed a global health hazard. While some vaccines have been developed, protection against viral infection is not perfect because of the urgent approval process and the emergence of mutant SARS‐CoV‐2 variants. Here, we employed UDCA as an FXR antagonist to regulate ACE2 expression, which is one of the key pathways activated by SARS‐CoV‐2 Delta variant infection. UDCA is a well‐known reagent of liver health supplements and the only clinically approved bile acid. In this paper, we investigated the protective efficacy of UDCA on Omicron variation, since it has previously been verified for protection against Delta variant. When co‐housing with an Omicron variant‐infected hamster group resulted in spontaneous airborne transmission, the UDCA pre‐supplied group was protected from weight loss relative to the non‐treated group at 4 days post‐infection by more than 5%–10%. Furthermore, UDCA‐treated groups had a 3‐fold decrease in ACE2 expression in nasal cavities, as well as reduced viral expressing genes in the respiratory tract. Here, the data show that the UDCA serves an alternative option for preventive drug, providing SARS‐CoV‐2 protection against not only Delta but also Omicron variant. Our results of this study will help to propose drug‐repositioning of UDCA from liver health supplement to preventive drug of SARS‐CoV‐2 infection.