Emerging technologies for the non-invasive characterization of physical-mechanical properties of tablets

The density, porosity, breaking force, viscoelastic properties, and the presence or absence of any structural defects or irregularities are important physical-mechanical quality attributes of popular solid dosage forms like tablets. The irregularities associated with these attributes may influence the drug product functionality. Thus, an accurate and efficient characterization of these properties is critical for successful development and manufacturing of a robust tablets. These properties are mainly analyzed and monitored with traditional pharmacopeial and non-pharmacopeial methods. Such methods are associated with several challenges such as lack of spatial resolution, efficiency, or sample-sparing attributes. Recent advances in technology, design, instrumentation, and software have led to the emergence of newer techniques for non-invasive characterization of physical-mechanical properties of tablets. These techniques include near infrared spectroscopy, Raman spectroscopy, X-ray microtomography, nuclear magnetic resonance (NMR) imaging, terahertz pulsed imaging, laser-induced breakdown spectroscopy, and various acoustic- and thermal-based techniques. Such state-of-the-art techniques are currently applied at various stages of development and manufacturing of tablets at industrial scale. Each technique has specific advantages or challenges with respect to operational efficiency and cost, compared to traditional analytical methods. Currently, most of these techniques are used as secondary analytical tools to support the traditional methods in characterizing or monitoring tablet quality attributes. Therefore, further development in the instrumentation and software, and studies on the applications are necessary for their adoption in routine analysis and monitoring of tablet physical-mechanical properties

Emerging technologies for the non-invasive characterization of physical-mechanical properties of tablets

The density, porosity, breaking force, viscoelastic properties, and the presence or absence of any structural defects or irregularities are important physical-mechanical quality attributes of popular solid dosage forms like tablets. The irregularities associated with these attributes may influence the drug product functionality. Thus, an accurate and efficient characterization of these properties is critical for successful development and manufacturing of a robust tablets. These properties are mainly analyzed and monitored with traditional pharmacopeial and non-pharmacopeial methods. Such methods are associated with several challenges such as lack of spatial resolution, efficiency, or sample-sparing attributes. Recent advances in technology, design, instrumentation, and software have led to the emergence of newer techniques for non-invasive characterization of physical-mechanical properties of tablets. These techniques include near infrared spectroscopy, Raman spectroscopy, X-ray microtomography, nuclear magnetic resonance (NMR) imaging, terahertz pulsed imaging, laser-induced breakdown spectroscopy, and various acoustic- and thermal-based techniques. Such state-of-the-art techniques are currently applied at various stages of development and manufacturing of tablets at industrial scale. Each technique has specific advantages or challenges with respect to operational efficiency and cost, compared to traditional analytical methods. Currently, most of these techniques are used as secondary analytical tools to support the traditional methods in characterizing or monitoring tablet quality attributes. Therefore, further development in the instrumentation and software, and studies on the applications are necessary for their adoption in routine analysis and monitoring of tablet physical-mechanical properties

Racial Variation in the Complexity of Coronary Artery Disease in Patients with Acute ST-Segment Elevation Myocardial Infarction

BACKGROUND: Racial variations in presentation of patients with ST-segment elevation myocardial infarction (STEMI) have been suggested. METHODS: This was a retrospective analysis of a tertiary center from 2012 to 2016. We included patients presenting with acute STEMI who received primary percutaneous coronary intervention (PCI). The main outcome was racial variation in the complexity of coronary artery disease assessed by SYNTAX score. We also reported predictors of higher SYNTAX scores in the study population. RESULTS: Our final analysis included 260 patients: 201 Whites (77.3%), 24 African Americans-AA (9.2%), 19 Hispanics (7.3%) and 15 were of other ethnicities (5.8%). The mean SYNTAX score was 13.8 ± 7.7. There was no significant difference between Whites, AA, Hispanics and other races in the SYNTAX score (13.8 ± 7.7, 13.4 ± 7.9, 14.5 ± 9 and 13.5 ± 6.6, p = 0.965). Logistic regression analysis identified chronic kidney disease as the only significant predictor of higher SYNTAX score (Coefficient = 3.5, 95%CI:0.41-6.60, p = 0.026), while no significant association was identified between different races and higher SYNTAX score. CONCLUSION: The current study did not identify racial variations in the complexity of coronary artery disease for STEMI patients. Further studies are needed at a larger scale to identify racial variations in STEMI patients

Meta-Analysis of Trials on Prophylactic Use of Levosimendan in Patients Undergoing Cardiac Surgery

BACKGROUND: The role of prophylactic levosimendan in patients undergoing cardiac surgery is controversial. METHODS: We performed a computerized search of Medline, Embase, and Cochrane databases through September 2017 for randomized trials evaluating the prophylactic use of levosimendan in patients undergoing cardiac surgery (ie, patients without low cardiac output syndrome). The main study outcome was mortality at 30 days. RESULTS: The final analysis included 16 randomized trials with total of 2,273 patients. There was no statistically significant difference in mortality at 30 days between levosimendan and control groups (relative risk 0.68, 95% confidence interval [CI]: 0.45 to 1.03). Subgroup analysis showed no statistically significant difference in mortality at 30 days for patients with reduced left ventricular ejection fraction compared with patients having preserved left ventricular ejection fraction (p for interaction = 0.12). Further analysis suggested that levosimendan might be associated with improved mortality at 30 days when compared with active-control but not when compared with placebo (p for interaction = 0.01). The levosimendan group had a significant reduction in acute kidney injury (relative risk 0.59, 95% CI: 0.38 to 0.92), intensive care unit stay (standardized mean difference = -0.21, 95% CI: -0.29 to -0.13), and ventilation time (standardized mean difference = -0.43, 95% CI: -0.61 to -0.25), whereas it had higher rates of atrial fibrillation (relative risk 1.11, 95% CI: 1.00 to 1.24). No statistically significant differences were observed between groups in mortality beyond 30 days, postoperative dialysis, or myocardial infarction. CONCLUSIONS: Prophylactic use of levosimendan does not appear to reduce the mortality at 30 days or beyond 30 days in patients undergoing cardiac surgery. This lack of benefit was noted irrespective of the LVEF

Design and evaluation of novel inhalable sildenafil citrate spray-dried microparticles for pulmonary arterial hypertension

Pulmonary delivery of vasodilators is a promising alternative for the intravenous and oral treatment of pulmonary arterial hypertension (PAH). The aim of this study was to design and evaluate hydrogel microparticles as a carrier for sustained pulmonary delivery of sildenafil citrate. Spray dried hydrogel microparticles containing biodegradable sodium carboxymethyl cellulose, sodium alginate, and sodium hyaluronate polymers at variable concentrations were prepared. A design of experiment using the “Extreme Vertices Mixture” design was executed. The design was used to study the influence of polymer concentration and their interactions on the physicochemical properties of the formulations in terms of particle size, particle size distribution, product yield, entrapment efficiency, and in-vitro drug release. Selected formulations were also evaluated for swelling, biodegradation, moisture content, in-vitro aerodynamic performance, and cytotoxicity. In addition, a lung deposition and pharmacokinetic study was conducted in rats to study drug accumulation in lungs and blood after intratracheal administration of the spray dried inhalable hydrogel microparticles in comparison to orally administered Viagra®. The results demonstrated that formulated microparticles had a mean geometric particle size between 2 and 5 μm, entrapment efficiency of \u3e80%, and yield ranging between 47 and 66% w/w. The in-vitro drug release profiles showed a sustained drug release of sildenafil citrate for over 24 h. The statistical design showed a significant influence of the microparticulate composition on the physicochemical properties. Furthermore, selected formulations were evaluated for their aerodynamic properties. The aerodynamic properties included fine particle fraction ranging between 24 and 30%, dose recovery percent of 68–8 5%, and average mass median aerodynamic diameter of 4.6–4.8 μm. The in-vivo pharmacokinetic study showed that inhaled spray dried hydrogel microparticles (M6) formulation had significantly higher lung/blood Cmax, AUC, extended half-life, and mean residence time in comparison to orally administered sildenafil citrate of the same dose. In conclusion, the formulated drug-loaded spray dried hydrogel microparticles showed promising in-vitro and in-vivo results for the pulmonary delivery of sildenafil citrate. The spray dried hydrogel microparticles formulation can be considered as a potential alternative of oral sildenafil citrate for treatment of PAH

Comparative Outcomes of Transapical Versus Transfemoral Access for Transcatheter Aortic Valve Replacement in Diabetics

INTRODUCTION: The outcomes of transfemoral (TF) compared with transapical (TA) access for transcatheter aortic valve replacement (TAVR) in diabetics are unknown. METHODS: We queried the NIS database (2011-2014) to identify diabetics who underwent TAVR. We performed a propensity matching analysis comparing TF-TAVR versus TA-TAVR. RESULTS: The analysis included 14.555 diabetics who underwent TAVR. After matching, in-hospital mortality was not different between TF-TAVR and TA-TAVR. (3.5 vs. 4.4%, p = 0.11). TF-TAVR was associated with lower rates of cardiogenic shock (2.7 vs. 4.7%, p = 0.02), use of mechanical circulatory support (2.0 vs. 2.9%, p = 0.03), acute renal failure (17.8 vs. 26.5%, p \u3c 0.001), major bleeding (35.8 vs. 40.7%, p \u3c 0.001) and respiratory complications (1.1 vs. 4.4%, p \u3c 0.001) compared with TA-TAVR. However, TF-TAVR was associated with a higher rate of vascular complications (2.9 vs. 0.9%, p \u3c 0.001), cardiac tamponade (0.5 vs. 0.0%, p \u3c 0.001), complete heart block (10.8 vs. 7.7%, p \u3c 0.001) and pacemaker insertion (11.8 vs. 8.3%, p \u3c 0.001). There was no difference between both groups in acute stroke (1.8 vs. 2.2%, p = 0.39), hemodialysis (2.0 vs. 2.2%, p = 0.71), and ventricular arrhythmias (4.9 vs. 4.2%, p = 0.19). Notably, TF-TAVR was associated with higher mortality, acute stroke, AKI, hemodialysis, PCI, and respiratory complications in complicated diabetics compared with non-complicated diabetics. CONCLUSIONS: This observational analysis showed no difference in-hospital mortality between TF-TAVR and TA-TAVR among diabetic patients. Studies exploring the optimal access for TAVR among diabetics are recommended