Development of Clinically Optimized Sitagliptin and Dapagliflozin Complex Tablets: Pre-Formulation, Formulation, and Human Bioequivalence Studies.

The purpose of this study is to derive an optimal drug release formulation with human clinical bioequivalence in developing a sitagliptin phosphate monohydrate-dapagliflozin propanediol hydrate fixed-dose combination (FDC) tablet as a treatment for type 2 diabetes mellitus. As a treatment for type 2 diabetes mellitus, the combined prescription of dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter-2 (SGLT-2) inhibitors is common. Therefore, this study simplified the number of individual drugs taken and improved drug compliance by developing FDC tablets containing sitagliptin phosphate monohydrate as a DPP-4 inhibitor and dapagliflozin propanediol hydrate as an SGLT-2 inhibitor.

Deubiquitinase catalytic activity of MYSM1 is essential in vivo for hematopoiesis and immune cell development.

Myb-like SWIRM and MPN domains 1 (MYSM1) is a chromatin binding protein with deubiquitinase (DUB) catalytic activity. Rare MYSM1 mutations in human patients result in an inherited bone marrow failure syndrome, highlighting the biomedical significance of MYSM1 in the hematopoietic system. We and others characterized Mysm1-knockout mice as a model of this disorder and established that MYSM1 regulates hematopoietic function and leukocyte development in such models through different mechanisms.

Development of Nafamostat Mesylate Immediate-Release Tablet by Drug Repositioning Using Quality-by-Design Approach.

We aimed to develop nafamostat mesylate immediate-release tablets for the treatment of COVID-19 through drug repositioning studies of nafamostat mesylate injection. Nafamostat mesylate is a serine protease inhibitor known to inhibit the activity of the transmembrane protease, serine 2 enzyme that affects the penetration of the COVID-19 virus, thereby preventing the binding of the angiotensin-converting enzyme 2 receptor in vivo and the spike protein of the COVID-19 virus. The formulation was selected through a stability study after manufacturing by a wet granulation process and a direct tableting process to develop a stable nafamostat mesylate immediate-release tablet.

In Vitro-In Vivo Correlation of Tianeptine Sodium Sustained-Release Dual-Layer Tablets.

Tianeptine tablets are currently marketed to be designed for immediate-release tablets. The tianeptine has a short half-life, making it difficult to design for sustained-release tablets and achieve bioequivalence with the tianeptine immediate-release tablet (Stablon). We established the in vitro-in vivo correlation (IVIVC) of three formulations of tianeptine sustained-release tablets according to their granule size.

Studies on Preformulation and Formulation of JIN-001 Liquisolid Tablet with Enhanced Solubility.

This study aimed to develop a heat shock protein 90 (Hsp90) inhibitor liquisolid tablet with improved solubility to overcome low bioavailability issues. As an active pharmaceutical ingredient (API), JIN-001, a novel Hsp90 inhibitor, was reported to have substantial in vitro antiproliferative and in vivo antitumor activity; however, JIN-001 was a crystalline solid with very low solubility in an aqueous solution, and therefore, Capryol 90, which has excellent solubilization ability, was selected as an optimal liquid vehicle based on solubility studies. JIN-001 liquisolid (JLS) powder was successfully prepared by dissolving JIN-001 in Capryol 90 and mixing colloidal silicon dioxide (CSD) used as an oil adsorption agent.

QbD Consideration for Developing a Double-Layered Tablet into a Single-Layered Tablet with Telmisartan and Amlodipine.

The aim of this study was to develop a single-layered version of commercially available Twynstar (Telmisartan + Amlodipine) double-layered tablets to improve the dosing convenience. A quality-by-design approach was applied to develop the single-layered version. To evaluate the range and cause of risks for a single-layered tablet in the formulation design research, we used the tools of the risk assessment, initial risk assessment of preliminary hazard analysis and main risk assessment of failure mode and effect analysis to determine the parameters affecting formulation, drug dissolution, and impurities.

Quality by Design Applied Development of Immediate-Release Rabeprazole Sodium Dry-Coated Tablet.

The aim of this study was to develop immediate-release oral rabeprazole sodium tablets with rapid efficacy and gastric stability for the treatment of gastroesophageal reflux disease. Rabeprazole sodium is a commonly prescribed proton pump inhibitor; however, it is extremely unstable and degrades in acidic environments. Hence, it has been manufactured and supplied only in enteric-coated tablet form, while immediate-release (IR) formulations for this drug are very limited.

Nanoporous Silica Entrapped Lipid-Drug Complexes for the Solubilization and Absorption Enhancement of Poorly Soluble Drugs.

This study aims to examine the contribution of nanoporous silica entrapped lipid-drug complexes (NSCs) in improving the solubility and bioavailability of dutasteride (DUT). An NSC was loaded with DUT (dissolved in lipids) and dispersed at a nanoscale level using an entrapment technique. NSC microemulsion formation was confirmed using a ternary phase diagram, while the presence of DUT and lipid entrapment in NSC was confirmed using scanning electron microscopy.

Nanotechnology in the arena of cancer immunotherapy.

Cancer immunotherapy orchestrates the immune system of the human body to fight against cancer cells. By doing this, it has revolutionized cancer treatment. Toxicities arising from dose-limit and low rates of patient response continue to be the major bottlenecks in clinical outcomes.

Preparation of Silica Microparticles as Volatile Material Carrier and Their Sustained-Release Property.

The aim of this study is to develop an effective delivery system (silica microparticles) encapsulating volatile essential oil (EO) by multiple emulsification process and sol-gel method. Depending on critical materials (Pluronic P123 and HPC) and process parameter (drying temperature), silica microparticles were prepared and evaluated. As results, the amount of EO inside microparticles increased in polymer-dependent manners.

Intraspecific variation and phylogeographic patterns of the grey-capped greenfinch . (Passeriformes: Fringillidae).

To study the intraspecific variation of the grey-capped greenfinch (Passeriformes: Fringillidae), we sequenced complete mitochondrial (mt) genome of the prevalent in Ulleung Island, Republic of Korea. The full length of the genome is 16,812 bp, containing 37 genes (2 rRNAs, 13 proteins, and 22 tRNAs) with a putative control region (D-loop). A total of 98 single nucleotide polymorphisms (SNPs) in the full mt genome were retained for Ulleung Island population and these SNPs were greater than those of inland population compared to the reference China subspecies.

Complete mitochondrial genome of the Grey-capped Greenfinch subspecies, (Passeriformes: Fringillidae).

We sequenced the complete mitochondrial (mt) genome of . The circular mt genome is 16,813 bp long and encodes 13 proteins, 22 transfer RNAs, and 2 ribosomal RNAs. Phylogenetic analysis based on full mt genome sequences confirmed that the is monophyletic group of the .

Quality-by-design approach for the development of telmisartan potassium tablets.

A quality-by-design approach was adopted to develop telmisartan potassium (TP) tablets, which were bioequivalent with the commercially available Micardis (telmisartan free base) tablets. The dissolution pattern and impurity profile of TP tablets differed from those of Micardis tablets because telmisartan free base is poorly soluble in water. After identifying the quality target product profile and critical quality attributes (CQAs), drug dissolution, and impurities were predicted to be risky CQAs.

Development of stabilized tenofovir disoproxil tablet: degradation profile, stabilization, and bioequivalence in beagle dogs.

The purpose of this study was to develop a hydrolysis-resistant optimized oral formulation of tenofovir disoproxil (TD) using a stabilizer. To develop a stabilized TD tablet bioequivalent to the commercial TD fumarate (TDF, Viread) tablet, TD free base was prepared and its degradation profile and stability were investigated. The TD tablet showed antiviral activity, but its absorption was limited in the intestinal tract because of premature degradation.

Improved Antitumor Efficacy of Hyaluronic Acid-Complexed Paclitaxel Nanoemulsions in Treating Non-Small Cell Lung Cancer.

Paclitaxel (PTX) is a effectively chemotherapeutic agent which is extensively able to treat the non-small cell lung, pancreatic, breast and other cancers. But it is a practically insoluble drug with water solubility less than 1 µg/mL, which restricts its therapeutic application. To overcome the problem, hyaluronic acid-complexed paclitaxel nanoemulsions (HPNs) were prepared by ionic complexation of paclitaxel (PTX) nanoemulsions and hyaluronic acid (HA) to specifically target non-small cell lung cancer.

Paclitaxel-loaded hyaluronan solid nanoemulsions for enhanced treatment efficacy in ovarian cancer.

Paclitaxel-loaded hyaluronan solid nanoemulsions (PTX-HSNs) were successfully fabricated for the delivery of PTX to improve ovarian cancer treatment via active tumor targeting. PTX-HSNs were fabricated using high-pressure homogenization with a microfluidizer and were lyophilized with d-mannitol. Hyaluronan was coated on the outside of the PTX-HSN sphere.

High paclitaxel-loaded and tumor cell-targeting hyaluronan-coated nanoemulsions.

The purpose of this study was to develop hyaluronan-coated nanoemulsions (HNEs) with high solubilizing capacity and tumor cell targeting capability for the poorly soluble paclitaxel. The HNEs were composed of dl-a-tocopheryl acetate, soybean oil, polysorbate 80, and ferric chloride and were coated with hyaluronic acid (HA) as a targeting moiety. The nanoemulsions (NEs) and HNEs with or without paclitaxel (PTX) were prepared using high-pressure homogenization with a microfluidizer and were lyophilized with d-mannitol.

Functional membrane-implanted lab-on-a-chip for analysis of percent HDL cholesterol.

A functional lab-on-a-chip has been developed for simultaneous quantitative analyses of high-density lipoprotein (HDL) cholesterol (HDL-C) and total cholesterol (total-C) in a submicroliter plasma sample. The analytical device was fabricated by placing commercial membranes, traditionally used for rapid diagnostics, within microfluidic channels engraved on the surface of a plastic chip. The concentration of HDL-C was measured using enzymatic reactions to produce a colorimetric signal after separation of the single plasma lipoprotein from a mixture.