Molecular dynamics of amorphous pharmaceutical fenofibrate studied by broadband dielectric spectroscopy$ / 药物分析学报

Fenofibrate is mainly used to reduce cholesterol level in patients at risk of cardiovascular disease. Thermal transition study with the help of differential scanning calorimetry (DSC) shows that the aforesaid active pharmaceutical ingredient (API) is a good glass former. Based on our DSC study, the molecular dynamics of this API has been carried out by broadband dielectric spectroscopy (BDS) covering wide temperature and frequency ranges. Dielectric measurements of amorphous fenofibrate were per-formed after its vitrification by fast cooling from a few degrees above the melting point (Tm ? 354.11 K) to deep glassy state. The sample does not show any crystallization tendency during cooling and reaches the glassy state. The temperature dependence of the structural relaxation has been fitted by single Vogel–Fulcher–Tamman (VFT) equation. From VFT fit, glass transition temperature (Tg) was estimated as 250.56 K and fragility (m) was determined as 94.02. This drug is classified as a fragile glass former. Deviations of experimental data from Kohlrausch–Williams–Watts (KWW) fits on high-frequency flank of α-peak indicate the presence of an excess wing in fenofibrate. Based on Ngai's coupling model, we identified the excess wing as true Johari–Goldstein (JG) process. Below the glass transition temperature one can clearly see a secondary relaxation (γ) with an activation energy of 32.67 kJ/mol.

A preliminary study of Heavy Brilliant Blue G for internal limiting membrane staining in macular hole surgery.

Context: Surgical outcomes of vitrectomy for idiopathic macular hole using a “heavy” Brilliant Blue G (HBBG) solution for staining and removal of the internal limiting membrane (ILM). Settings and Design: Prospective interventional case series conducted in a tertiary eye care hospital. Materials and Methods: Nineteen patients (20 eyes) with idiopathic macular hole were enrolled to undergo vitrectomy with ILM peeling using HBBG. BBG dye was made heavy by mixing with 10% dextrose normal saline (DNS) solution in 2:1 ratio. The adequacy of ILM staining was noted intraoperatively. The closure rates of macular hole and visual improvement were recorded. Patients were followed up postoperatively on day 1, week 1, and subsequently at 1, 3, and 6 months, and every 6th month thereafter. Statistical Analysis: Wilcoxon signed-rank test was used; P < 0.05 was considered significant. Results: Preoperative best-corrected visual acuity (BCVA) ranged from 20/1000 to 20/63 (median: 20/100). Intraoperatively, the ILM stained very well in all eyes, and was easily removed. All macular holes closed postoperatively. The mean follow-up was 6.15 ± 2 months (range: 4-10; median: 6 months). Final BCVA ranged from 20/20 to 20/80 (median: 20/40), amounting to a significant visual improvement (P = 0.0001). BCVA improved by 1-8 Snellen lines in 19 eyes (95%); 16 eyes (80%) improved by ≥2 lines; 13 eyes (65%) achieved a final BCVA of 20/40 or better. Conclusions: Addition of 10% DNS to BBG dye allowed good ILM staining with less dye during macular hole surgery, and provided excellent anatomic and visual outcomes.

Therapeutic Hypothermia for Neonatal Encephalopathy Implications for Neonatal Units in India.

Therapeutic hypothermia has recently emerged from bench to bedside. Three large multicenter trials from industrialized countries and three independent meta-analyses have shown its efficacy in reducing death and disability following neonatal encephalopathy due a perinatal hypoxic event. Many neonatal units in well-resourced settings now offer hypothermia as standard care in neonatal encephalopathy. However, these results cannot be extrapolated to low resource settings due to differences in population, risk benefits and high cost. Use of therapeutic hypothermia in low resource settings should be considered experimental and should therefore be restricted to well equipped level 2 and 3 neonatal units. The safety and efficacy of hypothermia using novel low technology methods need to be examined in rigorously controlled multicenter randomized controlled trials in these neonatal units before it can be offered as a standard care, as the risks may outweigh the benefits. The current practice of maintaining normothermia should continue, until such evidence is available.