Myung Joo Kang

Background/Objectives: The aim of this study was to design a nanosuspension (NS) of tegoprazan (TPZ), a novel potassium-competitive acid blocker (P-CAB), to overcome its low aqueous solubility and improve oral absorption. Methods: TPZ NSs were prepared using a lab-scale bead-milling technique. Subsequently, their physicochemical properties, in vitro dissolution profiles, storage stability, and in vivo pharmacokinetic profiles were evaluated. Results: Among various screened stabilizers, polyvinyl alcohol was selected as the suspending agent due to its favorable physicochemical stability. The optimized NS exhibited a mean particle size of approximately 270 nm and a zeta potential of −12.1 mV, preserving the crystalline state of TPZ. In vitro dissolution studies revealed that the NS and its freeze-dried form (NS-FD) markedly enhanced drug dissolution across all tested dissolution media (pH 1.2, 4.0, 6.8, and distilled water) compared to the raw drug material. Furthermore, the NS formulations remained physically and chemically stable for up to 12 weeks under long-term and accelerated storage conditions (25 °C/60% relative humidity (RH) and 40 °C/75% RH). In vivo pharmacokinetic studies in male Sprague–Dawley rats revealed that the oral TPZ NS resulted in approximately a 2.1-fold increase in systemic exposure compared to the raw material and microsuspension. Conclusions: These findings suggest that TPZ NS is a promising strategy to enhance the oral absorption of P-CAB, using a simple, organic-solvent-free fabrication process.

Tegoprazan (TPZ) is a promising potassium-competitive acid blocker, but its pH-dependent low solubility often leads to erratic oral absorption. Although several hydrophilic polymer-based amorphous solid dispersions have been attempted to enhance dissolution, they often suffer from thermodynamic instability or rely on complex, solvent-mediated manufacturing processes. Herein, to enhance dissolution and oral absorption, a crystalline drug-loaded melt granulation (MG) system using D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was fabricated while maintaining stable physicochemical properties. MGs were prepared via a solvent-free, hot-melt process by optimizing the type of solid surfactant carrier, the ratio of drug to solid surfactant, and the type and ratio of flow-enhancing excipients. The optimized composition was TPZ:TPGS:microcrystalline cellulose = 1:2:4 (w/w/w). Solid-state analyses revealed that TPZ was uniformly dispersed within the granules while retaining its crystalline form. Compared to the raw drug, the MG showed remarkably faster and higher dissolution across both acidic and neutral media. Under long-term (25 °C/60% RH) and accelerated storage conditions (40 °C/75% RH) for 24 weeks, MG exhibited robust physicochemical stability, showing no drug degradation, changes in dissolution behavior, or crystalline alterations. Moreover, in a pharmacokinetic evaluation in Sprague–Dawley rats, MG provided marked absorption enhancement, yielding over 1.8-fold increases in exposure compared to the raw material. Consequently, the crystalline drug-loaded TPGS-based MG represents a promising strategy for improving the oral delivery of TPZ.

Objectives: Fixed-dose combination tablets containing sitagliptin hydrochloride (SG) and metformin hydrochloride (MF) are a mainstay in the clinical management of type 2 diabetes. However, SG is highly susceptible to chemical degradation during storage, particularly in the presence of MF. Herein, a bilayer tablet in which SG and MF are physically separated into distinct layers was designed to enhance the chemical stability of SG while ensuring pharmacokinetic equivalence to the marketed reference product Janumet^®. Methods: The compositions of individual SG and MF compartments were selected based on evaluations of their physical properties and dissolution profiles. Critical process parameters, including the pre- and main compression forces and coating levels of bilayer tablets, were fine-tuned to achieve dissolution characteristics comparable to those of the reference product. Results: Under accelerated storage conditions (40 °C, 75% relative humidity), the optimized bilayer tablet exhibited superior stability, with total SG-related impurity levels of 0.18% compared with 0.86% in the reference product after six months. Furthermore, in a randomized bioequivalence study in healthy volunteers (n = 30), the SG/MF bilayer tablet was pharmacokinetically equivalent to the reference product, with all parameters falling within the Food and Drug Administration-mandated regulatory criteria. Conclusions: In conclusion, this SG/MF bilayer tablet has better storage stability than the reference product and may be an alternative to conventional SG/MF combination tablets.

Intratympanic (IT) injection of corticosteroids is a standard clinical treatment for sensorineural hearing loss; however, achieving both biocompatibility and efficient cochlea drug delivery remains a significant challenge. Herein, we engineered a novel drug nanocrystal (NS)-loaded thermo-reversible hydrogel (NS-TG) system of dexamethasone-21-palmitate (DEX-P), a lipophilic prodrug of dexamethasone (DEX), for improved IT delivery. NSs with a mean diameter of 835.0 nm were fabricated using a dual centrifugation process with polyvinyl alcohol as the stabilizer. The NS-TG system, comprising NSs in a 19% (w/v) Poloxamer 407 hydrogel, exhibited rapid gelation (2–3 min) and a 31-fold increase in drug solubility (1.57 ± 0.02 mg/mL) compared to NS alone, through micellar solubilization. In vitro cytotoxicity assays in HEI-OC1 cells revealed that NS-TG is highly biocompatible, maintaining cell viability, whereas the commercial lipid emulsion (Lipothason^®) induced significant cytotoxicity. In vivo pharmacokinetic evaluation in mice revealed that IT NS-TG provided superior cochlear drug absorption compared to DEX-SP solutions and DEX-P NS, despite showing lower absorption than the lipid emulsion. These findings suggest that the DEX-P NS-TG system, pending further investigation, could serve as a promising platform for cochlear steroidal delivery, offering an optimal balance between delivery efficiency and local safety for treating inner ear diseases.

This study investigated the antimicrobial potential of Coptis chinensis rhizome extract against key oral pathogens and evaluated the safety and clinical efficacy of a CCE-loaded mouthwash. CCE exhibited broad-spectrum bactericidal activity, with low minimum inhibitory concentrations (0.002–0.008%) and minimum bactericidal concentrations (0.004–0.016%) against Streptococcus mutans, Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis. Time-kill kinetics revealed that CCE promptly eradicated Porphyromonas gingivalis. To balance antimicrobial potency and sensory acceptability, specifically the extract’s bitterness, we established the CCE concentrations in the mouthwash at 0.01% and 0.02% (w/v). Preclinical safety evaluations in animal models, including oral mucosal irritation and skin sensitization tests, confirmed the biocompatibility of 0.02% CCE, yielding “None” and “Non-sensitizer” ratings, respectively. Furthermore, a four-week, randomized, double-blind clinical trial (n = 73) revealed that 0.02% CCE mouthwash substantially reduced halitosis-inducing volatile sulfur compounds (hydrogen sulfide by 59.5% and methyl mercaptan by 50.0%). Significant improvements were also observed in the Plaque Index (55.2% reduction), Gingival Index (52.0% reduction), and Bleeding on Probing (77.3% reduction), with no adverse effects. These findings provide preliminary evidence that CCE mouthwash improves halitosis-related parameters and gingival indices in adults with self-reported halitosis, though further research is required to evaluate its long-term impact on broader periodontal disease states.

This study designs stable fast-disintegrating oral granules (FDGs) of volatile liquid essential oils (cinnamon, lemon, rose, and peppermint oils) for olfactory rehabilitation. By adsorbing liquid-type essential oils onto colloidal silicon dioxide (1:1 w/w) and incorporating olive oil (1:1:0.25 w/w) as a volatile restrainer, the retention of major odorants—cinnamaldehyde, citral, phenethyl alcohol, and menthol—in cinnamon, lemon, rose, and peppermint oils, respectively, was markedly improved after 12 h of exposure at 40 °C. Then, free-flowing FDG system was formulated with sugar alcohols (mannitol, xylitol, and sorbitol), low substituted hydroxypropyl cellulose, and magnesium stearate, exhibiting rapid spreading and disintegration (82% of cinnamaldehyde, citral, phenethyl alcohol, and menthol for 8 weeks under 25 °C/65% relative humidity (RH) conditions. In an in vitro volatilization test, major odorants were effectively volatilized from artificial saliva-wetted FDGs within 90 min depending on the volatility of each constituent. Therefore, this novel oral FDG system is expected to be a promising alternative for olfactory training for neurogenic smell dysfunction, providing enhanced storage stability, precise dosing, and patient compliance.

Poly(lactic-co-glycolic acid) (PLGA) sustained-release systems for intra-articular (IA) delivery aim to extend joint residence time and reduce the reinjection frequency of conventional IA therapies. This review synthesizes current understanding of PLGA degradation, the acidic microenvironment inside degrading microspheres, and release behavior in joints, and surveys clinical experience with extended-release corticosteroid depots alongside emerging platforms for nonsteroidal and biologic agents. To situate PLGA within the broader IA field, we briefly summarize selected non-PLGA sustained-release approaches—such as multivesicular liposomes, hyaluronic acid conjugates, and hybrid matrices—to contextualize comparative performance and safety. For proteins and peptides, central barriers include acidification inside degrading microspheres, aggregation during fabrication and storage, and incomplete or delayed release, as illustrated by glucagon-like peptide-1 analog formulations. Mitigation strategies span pH buffering, excipient-based stabilization, and gentler manufacturing that improve encapsulation efficiency and preserve bioactivity. Translation hinges on manufacturing scale-up and quality systems that maintain critical particle attributes and enable informative in vitro–in vivo interpretation. Clinically, prolonged symptom relief after single dosing has been demonstrated for corticosteroid depots (e.g., ~50% pain reduction over 12 weeks with a single PLGA–triamcinolone injection), whereas repeat-dose safety and indication expansion beyond the knee remain active needs best addressed through multicenter trials incorporating imaging and patient-reported outcomes. Consistent real-world performance will depend on controlling batch-to-batch variability and implementing pharmacovigilance approaches suited to long dosing intervals, enabling broader clinical adoption.