Vijay Kotra

The growing number of pandemics and emergencies traversing the world in recent decades has illustrated the vulnerability of the conventional pharmaceutical development process and the necessity of an efficient, robust, and patient-driven pandemic-ready development model. QbD is a scientifically proven proactive approach that has been comprehensively examined recently for its potential to effectively optimize formulations in an accelerated time frame. Risk factor assessment and constant surveillance serve to maintain the product quality & standards before the final stage of large-scale production and offer regulatory pliability. The extension of this method, AQbD, paired side by side also assists in accelerated assessment and quality assurance which is a critical component in any global circumstance. In recent years studies have been done by applying this novel approach, but very little has been reported on the establishment of this approach as a Pandemic-Ready Development Framework. This mini review addresses the regulatory basis alongside the key principles of QbD, which aligns its working approach as optimally compatible with any pandemic situation. Furthermore, it emphasizes the widespread implementation of this approach as AQbD, which stands for swift testing coupled with quality assurance standards. It also focuses on the limitations and critical areas where QbD can be applied to cope with existing demands in near future. Further, it applies this approach in several formulation developments pertinent to pandemic or endemic conditions and discusses the challenges of implementation and future directions. Overall, this discussion stresses the potential of this approach as a very promising framework for future pandemics.

The bacterium Borrelia burgdorferi is the source of the complicated tick-borne sickness known as Lyme disease. It is essential to accurately categorize Lyme disease into its many stages and symptoms to assist with treatment choices and enhance patient outcomes. In the proposed work, a unique method for categorizing Lyme illness into 15 different classifications by combining the features of Bandelet transform with Convolutional Neural Networks (CNN) which are employed to learn and categorize the discriminative features that were extracted from medical images. Therefore, multiresolution features are extracted using Bandelet Transform. Statistical Texture features such as Mean, Variance, Standard Deviation, Kurtosis and Skewness are calculated from the coefficients of Bandelet Transform which are concatenated with the features extracted from the different pre-trained networks. For the balanced dataset, using EfficientNet-B0 combined with Bandelet transform achieved an IBA of 0.974 and test accuracy of 0.9868. For the unbalanced dataset, using EfficientNetV2B1 with Bandelet transform resulted in an IBA of 0.932 and test accuracy of 0.9812. When classifying the images into 15 different classes, EfficientNetB7 with Bandelet transform achieved an IBA of 0.6424 and test accuracy of 0.7925. The results demonstrate that concatenating pretrained network features with Bandelet transform features improves classification performance for binary classification tasks (balanced and unbalanced datasets), though performance is more limited when extending to 15-class classification.

Background: Seeds of plant Scaphium affine are traditionally used by the healers of “In-dia” for the treatment of piles. Objectives: The primary objective of the study was to assess the anti-hemorrhoidal potential of the ethanolic seed extract of Scaphium affine. Methods: After the soxhlet extraction method, the seed extract from Scaphium affine was first sub-mitted to phytochemical standardization and then GC-MS analysis. Rats were given Croton oil and Jatropha oil to develop hemorrhoids, and Scaphium affine seed extract (ESA) was administered orally for 5 days and 3 days, respectively, at doses of 1000 and 500 mg/kg. The Rectoanal coefficient (RAC) was calculated as an inflammatory marker. The hemorrhoidal tissues were also subjected to cytokine profiling, biochemical estimation and histopathology. Results: ESA demonstrated the presence of flavonoids, saponins, phytosterols, phenols, and tannins. GCMS analysis elucidated the presence of hexadecanoic acid 2 hydroxy -1,3 propane diyl ester,9 Octadecanoic acid ethyl ester, Cyclohexane 1,4 di methyl cis, Farnesol isomer,1, E-11, Z-13 octa decatriene, Stigmasterol, N-(5 ethyl -1,3,4-thiadiazol-yl) benzamide, N, N Dinitro 1,3,5,7 tetraza bicyclo 93,3,1) as major phytoconstituents. The results depicted more potent anti-hemorrhoidal ac-tivity of ESA at 1000 mg/kg, p.o., which was evident through a decrease in RAC. A significant decline in the levels of IL-1β, IL-6, and TNF-α expression was observed, along with the restoration of altered antioxidants and enzymes. Histopathological analysis confirmed the tissue recovery as it revealed minimal inflammation and decreased dilated blood vessels in treated animals. Conclusion: Based on the results it can be concluded that seeds of Scaphium affine showed signifi-cant anti-hemorrhoid agents which may be attributed to their anti-inflammatory and anti-oxidant potential due to the presence of certain phytoconstituents in it. The study also supports the traditional use of seeds of Scaphium affine for the first time in the treatment of hemorrhoids.

Chalcones have been well examined in the extant literature and demonstrated antibacterial, antifungal, anti-inflammatory, and anticancer properties. A detailed evaluation of the purported health benefits of chalcone and its derivatives, including molecular mechanisms of pharmacological activities, can be further explored. Therefore, this review aimed to describe the main characteristics of chalcone and its derivatives, including their method synthesis and pharmacotherapeutics applications with molecular mechanisms. The presence of the reactive α,β-unsaturated system in the chalcone’s rings showed different potential pharmacological properties, including inhibitory activity on enzymes, anticancer, anti-inflammatory, antibacterial, antifungal, antimalarial, antiprotozoal, and anti-filarial activity. Changing the structure by adding substituent groups to the aromatic ring can increase potency, reduce toxicity, and broaden pharmacological action. This report also summarized the potential health benefits of chalcone derivatives, particularly antimicrobial activity. We found that several chalcone compounds can inhibit diverse targets of antibiotic-resistance development pathways; therefore, they overcome resistance, and bacteria become susceptible to antibacterial compounds. A few chalcone compounds were more active than conventional antibiotics, like vancomycin and tetracycline. On another note, a series of pyran-fused chalcones and trichalcones can block the NF-B signaling complement system implicated in inflammation, and several compounds demonstrated more potent lipoxygenase inhibition than NSAIDs, such as indomethacin. This report integrated discussion from the domains of medicinal chemistry, organic synthesis, and diverse pharmacological applications, particularly for the development of new anti-infective agents that could be a useful reference for pharmaceutical scientists.

Abnormal production of pro-inflammatory mediators and generation of reactive oxygen species (ROS) play a key role in the development and progression of various human disorders. The study aims to investigate the in vitro anti-inflammatory and antioxidant activity of 4-allyl pyrocatechol (4-APC) and its derivatives (APC-1 and APC-2) by albumin denaturation and 1,1-Diphenyl-2-picrylhydrazyl (DPPH) methods, respectively. Also, the test compounds are studied in silico for their inhibitory potential against the pro-inflammatory and oxidative markers (calpain, FAAH, and TNF-α) via molecular docking. The compounds have exhibited appreciable in vitro anti-inflammatory and antioxidant activities. The APC-2 compound has demonstrated significant anti-inflammatory and antioxidant activity (percentage inhibition = 69±0.76 and 77.05±0.92, respectively, at 100 μg/ml) compared to the standard drugs, aspirin and ascorbic acid (percentage inhibition = 82±0.83 and 92.35±0.75, respectively, at 100 μg/ml). The docking study has showed that APC-2 significantly inhibited calpain (PDB ID: 2R9C), FAAH (2WJ1) and TNF-α (2AZ5) inflammatory markers. The drug-likeness, bioactivities, ADME profile (pharmacokinetic) and toxicity properties have also been determined using online tools (Molinspiration, pkCSM, SwissADME, PreADMET). The test compounds have showed acceptable drug-likeness, bioactivity score, ADME and toxicity properties. Finally, we conclude that the 4-allylpyrocatechol and its derivatives can be used as lead molecules for their further development as therapeutically useful anti-inflammatory agents.

Chemotherapeutics and biotherapeutics agents have been explored as a potential treatment for COVID-19. This study was aimed to elucidate latest update related to biotherapeutics and chemotherapeutics against COVID-19 and its variants as well as the product specifications and marketing dynamics of its pharmacotherapies. There are several chemotherapeutics that have been studied for the treatment of COVID-19, including Paxlovid (Nirmatrelvir & Ritonavir) fixed dose combination, nirmatrelvir and ritonavir fixed dose combination, Remdesivir (Vekulary/Covifor) fixed dose combination, chloroquine and hydroxychloroquine, molnupiravir, favipiravir, Infliximab (Remsima®) fixed dose combination tocilizumab (Actimera), casirivimab+imdevimab (Ronapreve) fixed dose combination, ivermectin, methylprednisole. These drugs have been repurposed for use in COVID-19 due to their antiviral properties and ability to reduce inflammation. The COVID-19 death cases have significantly reduced because of tested efficacy of advanced biotherapeutics and chemotherapeutics. As for marketing dynamics, the demand for chemotherapeutics for the treatment of COVID-19 has increased significantly since the outbreak of the pandemic. Hence, the prices of anti-viral and monoclonal antibodies in top COVID-19 affected countries is also presented here. Considering the molecular interactions, therapeutic activity, efficacy, and adverse effects, the USFDA and the WHO recommended the aforementioned drugs. The chances of approval seems favouring biotherapeutics as these have the best characteristics among the chemotherapeutics. Overall, this review contributes to the scientific understanding of the COVID-19. This can help to inform future research and development efforts and contribute to the overall advancement of knowledge in the field of medicine.

A series of novel indole quinoline derived chalcones were synthesized using cost-effective synergetic catalytic system consisting of heterogeneous basic bleaching earth clay (pH 12.5) and PEG-400 as solvent at ambient temperature with the yields of 60-76%. All these chalcones were characterized by spectral data. Both the DPPH and SOR scavenging assays were performed to evaluate their antioxidant nature of these compounds.

Chromatography is a widely used analytical tool for separating a mixture of compounds into individual component. High performance liquid chromatography (HPLC) is one of the most important methods used for the separation, identification and quantification of a compounds present in a mixture. It meets many criteria of analysis but its main drawbacks are it is relatively time consuming to run a chromatogram and consumes high amount of solvent compared to other analytical methods. There is a need to develop a method which can overcome these drawbacks of HPLC. Ultra performance liquid chromatography (UPLC) is the new approach which opens novel direction in the field of liquid chromatography. It works on similar principle but shows better performance than conventional HPLC. UPLC is a technique of liquid chromatography with improved runtime and sensitivity with less than 2 μm particle size. The UPLC separation process is carried out under very high pressure (up to100 MPa). Additionally, it reduces the cost of reagent with shorter run time as compared to conventional HPLC. This article updated until 2020, provides a general review on the principle, instrumentation and application of UPLC in different fields of science.