Equivalent Method Development and Cross Validation of Pharmacopoeial Method of Montelukast Sodium

The purpose of this exploration research work article is to develop equivalent method and evaluate its equivalency (Cross validation) against pharmacopoeial method of Montelukast sodium for the evaluation and assessment of process related impurities i.e. Methyl MLK impurity in Montelukast sodium by HPLC method and its principles. The method mentioned in European Pharmacopoeia (EP) and United States Pharmacopoeia (USP) does not sufficiently separates impurity C and impurity D , as these impurities elutes under the main peak and the pharmacopoeial methods were also not able to detect the Methyl MLK impurity which is not listed in USP monograph. So our prime design of experiment is to develop of new high-performance liquid chromatographic (HPLC) method which eliminates the drawback of two pharmacopoeial methods and this proposed created strategy is fit for recognition and detection of Methyl MLK impurity and separation of all process related impurities of Montelukast sodium mentioned in EP and USP monographs. An efficient strategy screening and scouting in which various C-18 columns were tried and tested. LUNA C-18 column utilized in RP HPLC mode ended up being the phenomenal decision for the technique streamlining. The proportion of acetonitrile and trifluoroacetic acid (TFA) in water and in the mobile phase, column temperature, flow rate and diluents were considered as basic strategy boundary. The method developed equivalency was checked in terms of Specificity, LOD, Quantitation (LOQ), Precision, Linearity, Relative response factor (RRF), and Accuracy.

Application of Design of Experiment in Design, Development and Optimization of Stability Indicating RP-HPLC Method for Simultaneous Determination of Montelukast Sodium and Rupatadine Fumarate in Bulk and Formulation

Design of Experiment assisted stability indicating RP-HPLC wasdesigned, developed and optimized using response surface methodology for simultaneous determination of Montelukast sodium and Rupatadine fumarate. Separation was achieved using Acetonitrile: Phosphate buffer (75:25) v/v with pH adjusted to 4.0, flow rate of 1 ml/min with UV detection at 246 nm on RP-C18 column. Stress degradation studies were performed as per scientific guidelines. Method was validated in accordance with regulatory requirements. Results obtained in validation were found to be within specified limit. Montelukast was eluted at 3.99 min and Rupatadine was eluted at 13.25 min respectively. All stress degradation products are very well resolved from drug peak which indicate suitability indicating nature of the developed method. Design of Experiment technique can help in fast and economical optimization of mobile phase which in turn will save time for method development. The developed method is, accurate, sensitive which can be utilized as stability indicating method for identification of degradation products in routine analysis of the drug.

Drug targeting Nsp1-ribosomal complex shows antiviral activity against SARS-CoV-2

The SARS-Cov-2 non-structural protein 1 (Nsp1) contains an N-terminal domain and C-terminal helices connected by a short linker region. The C-terminal helices of Nsp1 (Nsp1-C-ter) from SARSCov-2 bind in the mRNA entry channel of the 40S ribosomal subunit and block the entry of mRNAs thereby shutting down host protein synthesis. Nsp1 suppresses the host immune function and is vital for viral replication. Hence, Nsp1 appears to be an attractive target for therapeutics. In this study, we have in silico screened Food and Drug Administration (FDA)-approved drugs against Nsp1-C-ter and find that montelukast sodium hydrate binds to Nsp1-C-ter with a binding affinity (KD) of 10.8±0.2 μM in vitro and forms a stable complex with it in simulation runs with a binding energy of - 76.71±8.95 kJ/mol. The drug also rescues the inhibitory effect of Nsp1 in host protein synthesis as demonstrated by the expression of firefly luciferase reporter gene in cells. Importantly, montelukast sodium hydrate demonstrates antiviral activity against SARS-CoV-2 with reduced viral replication in HEK cells expressing ACE2 and Vero-E6 cells. We therefore propose montelukast sodium hydrate may help in combatting SARS-CoV-2 infection.

Clinical Analysis of Dispelling Wind, Eliminating Lung and Relieving Cough Combined with Western Medicine in the Treatment of Cough Variant Asthma in Children

Objective: This study mainly explores the clinical effect of dispelling wind, eliminating lung and relieving cough combined with western medicine in the treatment of cough variant asthma. Methods: 80 children with cough variant asthma accepted by our hospital from January 2018 to December 2020 were randomly selected for the study and divided into two groups. One group was the reference group (40 cases) treated with procaterol hydrochloride tablets and montelukast sodium, and the other group was the research group (40 cases). The method of eliminating wind, eliminating lung and relieving cough was combined with procaterol hydrochloride tablets and montelukast sodium to observe and compare the curative effects of the two groups. Results: There was no significant difference in TCM symptom score and eosinophil (EOS) count between the two groups before treatment (P > 0.05); After treatment, the TCM symptom scores of coughs, pharyngeal itching, expectoration, nasal congestion and nasal itching in the research group were lower than those in the reference group, and the EOS count was lower than that in the reference group (P < 0.05); The effective rate of research group was higher than that of reference group (P < 0.05). Conclusions: For children with cough variant asthma, Qufeng Sufei cough relieving method combined with procaterol hydrochloride and montelukast sodium can improve children’s symptoms and reduce eosinophil count.