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QbD Driven Approach for Method Development and Validation for The Determination of Gilteritinib By RP-HPLC

Quality by Design (QbD) assisted approach was used for development of robust and rugged RP-HPLC method and validated as per ICH guidelines. Methods developed using QbD approach are highly robust, cost effective, uses good experimental designs, have shorter run times, optimization can be done by statistical analysis and can be easily validated compared with the traditional methods developed by one-factor-at-a-time (OFAT) approach. Central-composite design (CCD) under Response Surface Methodology (RSM) was used for development of optimized method based on desirability functions approach. The factors selected for the present study were % organic composition in mobile phase, column temperature, flow rate and responses investigated were retention time of the drug and theoretical plate count. Chromatographic separation was achieved using Phenomenex C18 (150 mm x 4.6 mm, 5) column. Statistical analysis of CCD experimental data was done by applying ANOVA and the selected mathematical models for the responses were found to be significant with p < 0.05. The optimized conditions based on highest desirability value of 1 was achieved using Acetonitrile: Phosphate buffer (42.1: 57.9% v/v) mobile phase pumped at 0.93ml/min flow rate at 31.70C. The drug eluted at a retention time of 2.655 min. Finally the developed method was validated according to ICH Q2 (R1) guidelines. All the system suitability parameters were found to be within the limits. Forced degradation studies were performed according to ICH guidelines with notable degradation found in acidic condition.

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Early Versus Late Trans Catheter PDA Closure : Effect on LV Remodelling and Recovery Post Closure

Background There is paucity of data concerning the hemodynamic effect of delayed trans-catheter patent ductus arteriosus (PDA) closure. The current study tried to address this issue Methods This was a prospective observational study including 42 patients with mean age of 48 months and mean PDA diameter of 2.7±0.8 mm. The study group was subdivided into 2 subgroups (1st group less than and 2nd group more than 2 years of age at time of PDA closure). The 2 groups were assessed regarding the impact of PDA closure on different LV parameters measured by trans thoracic echocardiogram (2D dimensions, systolic function and 2D speckle tracking). Results LVEF in both groups decreased significantly immediately post PDA closure (p> 0.0001), but at 3 months follow up only in older group did it continue to be significantly lower than baseline values (p> 0.002). In group 1, indexed LVEDV and LVESV demonstrated significant early and continuous improvement at immediate and 3 months follow up (p>0.0001). Group 2 demonstrated only late improvement at 3 months follow up in indexed LVESV. GLS in both groups dropped significantly immediately post closure with significant improvement at 3 months follow up but GLS values remained significantly lower in group 2 compared to group 1 (p> 0.006). In both groups, age was positively correlated with percent reduction in GLS immediately post PDA closure and was negatively correlated with percent increase in GLS from immediate to 3 months follow up (degree of recovery). PDA size was negatively correlated with percent increase in LVEF from immediate to 3 months follow up (degree of recovery) Conclusion Trans catheter PDA closure in children 2 years old or less was associated with early reduction in LVEDV, LVESV, and greater improvement in LVEF and GLS after initial drop. It is crucial to diagnose and close hemodynamically significant PDAs as early as possible to ensure better LV reverse remodelling.

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Healthcare Workers’ Perceptions of Pharmaceutical Quality Assurance in Reducing Medication Errors: A Systematic Review

Background: Medication errors is a major problem in today’s health facilities because the blunders resulting to more doom to patent, time wastage, and high costs to the healthcare system. Current medical practices should effectively control such mistakes to avoid compromising the lives of patients; pharmaceutical quality assurance plays a critical role in avoiding these errors; however, there is scarce literature on how different health care providers view and adapt the practices. Aim: This systematic review seeks to look at the views that various healthcare worker groups will have concerned the role of pharmaceutical QA in decreasing the rates of MEs among doctors, nurses, pharmacists, pharmacy technicians, and healthcare quality assurance specialists. Method: Among the ten studies undertaken, attempts were made to look for themes that where pertinent to Healthcare Workers perceptions of QA practices. In order to offer a qualitative synthesis of the studies, the relationship between medication error prevention and QA across the healthcare professions was sought, through identifying recurring themes, trends, and findings. Results: These findings are consistent with other studies that people’s perceptions depend on the nature of their job. Resident pharmacists and pharmacy technicians supported, suggesting that there should be clarity regarding QA to reduce dispensing errors. A major concern addressed by the nurses was workload which affected QA as well as leadership support provided in the health centers. Among doctors, even those who paid attention to the patient outcome found QA practices useful, except that clinical workload was reported as a source of stress. The healthcare quality assurance specialists described the benefits of Total Quality Management (TQM), distinguishing it from QM, in minimizing errors across the professions. Amongst them, leadership quality was found to play a pivotal role along with role clarification and organizational workload. Conclusion: This study confirms that leadership support, role appropriate involvement and support are the cornerstone of good pharmaceutical QA in healthcare facilities. Analyzing the differences between each position is necessary to develop ways to boost medication security and decrease errands.

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Antiviral Potency of Antipsychotics: A New Therapeutic Strength

The rationale behind alternative medicine is to repurpose existing medicines to meet unmet medical needs. Antipsychotics, originally developed to treat mental disorders such as schizophrenia and bipolar disorder, are now being evaluated for broader therapeutic potential. From safety data and known mechanisms of action, scientists are testing the effects of antipsychotics (APs) on viruses as a consequence to the lack of successful antivirals available. For example, some APs inhibit viral replication, prevent viral entry into host cells, or modulate immune responses. However, pre-experimental and clinical studies are needed to validate these findings. Drug repurposing has been a promising strategy, specifically after the devastating COVID-19 pandemic. We created this systematic review aiming to gather reliable scientific evidence to help examine the success of repurposing antipsychotics as possible candidates for numerous viral infections, particularly SARS- CoV2 infection. As of August 2024, we carried out random effect meta-analysis on many clinical studies where most studies provided data supporting the beneficial effect of repurposing APs as antivirals for COVID-19 treatment. On the contrary, one study provided data showing that APs increased the risk of severe COVID-19 and mortality; even though, their use should be examined case by case and psychiatric patients should not be encouraged to discontinue their psychiatric treatment. Based on numerous studies, we observed that AP drugs of the phenothiazine class (promethazine, fluphenazine, chlorpromazine, and thiethylperazine) display a unique pharmacological profile to convergently inhibit SARS-CoV-2. Interestingly, only the phenothiazine class contained at least 10 drugs matching criteria for antiviral effects against SARS- CoV-2. In addition to their efficacy as antipsychotics (and antiemetics in certain cases), this class of agents has also shown antiviral, antibacterial, and anti-prion activities in previous in vitro studies. Therefore, drug repurposing of APs could be a great chance to combat several viral infections while bypassing long-term drug development and providing rapid solutions to emerging health challenges.

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A Novel Eco-Friendly Approach using the Concept of Hydrotropy for Analytical Estimation of Mirtazapine by HPLC used to Treat Depression

Introduction: In the pharmaceutical field, it is often required to prepare aqueous solutions of a variety of insoluble drugs. The ability to increase aqueous solubility can be a valuable aid for increasing the efficacy and reducing adverse effects for certain drugs. Most quantitative analyses of poorly water-soluble drugs involve the use of various organic solvents. Hydrotropic solutions may be a proper choice to preclude the use of organic solvents, providing a simple, accurate, novel, safe, and precise method for drug analysis. Objective: Current research work includes development and validation of ecofriendly HPLC method using the novel concept of Hydrotropy for analytical estimation of Mirtazapine with comparative greenness with literature method. Methodology: The method was developed using 0.2% Ortho phosphoric acid in water as the mobile phase and Xterra C18 (250mm*4.6mm) 5μm column. The flow rate was set to 1.0 mL/min, and detection was done at 314 nm. Results: The linearity range of 50%-150% met the correlation coefficient > 0.998. The %RSD for method precision was < 2.0%. The recovery range of 50-150% met 98-102%. Conclusion: Hydrotropic method developed was successfully validated as per ICH Q2 (R1) with sufficient Specificity, Linearity, Accuracy and Precision. Additionally, the developed method was greener and ecofriendly compared to other literature method.

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