gemigliptin + metformin hydrochloride (ZemiMet / ZemiMet SR)

Development of propranolol hydrochloride extended-release lipid matrix tablets for pediatric use.

Broocks Stefanie S, Gebhardt Melanie M, Klein Sandra S

Although solid oral dosage forms are widely used in adult drug therapy, age-appropriate formulations for pediatric patients remain limited. The development of suitable dosage forms is challenged by specific requirements regarding excipient safety, tablet size, and dose flexibility, as well as the need to improve therapy adherence in the context of frequent dosing. This study aimed to develop a pediatric-appropriate extended-release matrix tablet based on lipid matrix formers, with particular attention to the use of safe excipients and the selection of excipients based on sustainability considerations. Lipid-based excipients, selected due to their natural origin and similarity to dietary fats, were investigated and compared with conventional matrix formers. A formulation screening approach was applied to identify promising candidates based on drug release after one hour, followed by further evaluation of manufacturability, tablet hardness, and extended-release performance. In addition, the influence of a physiological pH-gradient, bile salts, and long-term storage on drug release was assessed. The selected formulations showed good manufacturability, uniformity, and sustained drug release. Overall, several lipid-based matrix formulations suitable for pediatric use were identified, providing a promising basis for the development of solid oral extended-release dosage forms for children.

Cumulative Metformin Use and Hepatocellular Carcinoma Risk After HCV SVR: A Multicentre Cohort Study.

Calvo-Sánchez Henar H, Jara-Fernández Lorena L, Encijo-Heredia Raquel R, Villarino Irene I et al.

Although sustained virological response (SVR) after hepatitis C virus treatment reduces hepatocellular carcinoma (HCC) incidence, residual risk persists. Metformin has been associated with lower HCC risk, but whether cumulative metformin exposure (CME) lowers post-SVR risk remains unclear. We evaluated whether CME was associated with lower HCC risk after SVR. We analysed a multicentre cohort of 1531 patients who achieved SVR after direct-acting antiviral therapy (median follow-up, 75.5 months). Metformin exposure was modelled as a time-updated cumulative variable in start-stop Cox models to control for immortal-time bias. Stabilised inverse probability weighting addressed confounding by indication and censoring. The overall model was sex-stratified and adjusted for FIB-4, clinically significant portal hypertension (CSPH), type 2 diabetes mellitus (T2DM) and smoking. A prespecified T2DM-restricted analysis used T2DM-specific IPTW plus IPCW, sex stratification and CSPH adjustment. During follow-up, 50 patients developed HCC. Crude incidence was highest among patients with FIB-4 > 3.25, CSPH and T2DM without metformin exposure (4.84 cases per 100 person-years). In the overall weighted model, CME was associated with lower HCC risk (HR, 0.46 per year; 95% CI, 0.27-0.77; p = 0.004). CSPH, T2DM, smoking and FIB-4 > 3.25 independently increased risk. In the T2DM-restricted model, each additional year remained associated with lower HCC hazard (HR, 0.49; 95% CI, 0.29-0.84; p = 0.009), whereas CSPH was associated with higher risk (HR, 6.04; 95% CI, 2.12-17.19; p < 0.001). After SVR, CME was associated with lower HCC risk; this possible duration-dependent inverse association was clinically interpretable only among metformin-eligible patients with T2DM.

Insulin Resistance is Not a Predictor of Response to Low-Dose Oral Metformin Therapy in Patients with CCCA: A Retrospective Review.

Adedeji Opemipooluwa O, Aguh Crystal C

Controlled release network hydrogel based on zein/sodium alginate-stabilized chrysanthemum essential oil Pickering emulsions for prolonged preservation of fresh-cut Gastrodia elata.

Zhang Lihui L, Liu Jieni J, Law Chung Lim CL, Sun Qing Q et al.

Browning and microbial proliferation are major factors driving quality deterioration in fresh-cut Gastrodia elata. This study developed a zein/sodium alginate-stabilized chrysanthemum essential oil (CEO) Pickering emulsion and incorporated it into gelatin-konjac glucomannan hydrogels for fresh-cut G. elata preservation. The emulsion exhibited nanoscale droplets (194.53-515.00 nm) with exceptional stability (zeta potential: -82.85 to -95.92 mV), confirming effective encapsulation of CEO. The optimized hydrogel (GK-8%) formed a dense network with uniform pore structure, demonstrating superior water retention and sustained release properties, achieving 73.30% CEO release over 390 h. Application tests revealed that GK-8% significantly reduced weight loss (≤ 0.15%) and browning index (26.72% reduction), maintained firmness and total phenolic content, while decreasing antioxidant enzyme activities, indicating reduced oxidative stress. Visual observations showed that GK-8% treatment delayed visible browning by approximately 3 days compared to the control. The hydrogel extended shelf life through synergistic effects of microbial inhibition and oxidative stress alleviation, providing an effective, eco-friendly strategy for fresh-cut product preservation.