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Cefpodoxime proxetil (CPDX-PR) is an oral cephalosporin antibiotic with poor aqueous solubility and bioavailability. Effect of -cyclodextrin on aqueous solubility and dissolution rate of cefpodoxime proxetil was evaluated by the formation of solid inclusion complexes in 1:2 molar ratio of drug: cyclodextrin. Phase solubility study was carried out whereby a typical B's type curve was obtained thus, indicating a 1:2 stoichiometric ratio for optimum complex formation. Solid inclusion complexes in 1:2 molar ratios were prepared by using methods such as physical mixture, solvent evaporation and freeze drying. Prepared complexes were characterized by fourier transform infrared spectroscopy (FT-IR) differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD) and scanning electron microscopy (SEM). Results of in vitro studies appraised of an increased solubility and dissolution rate of cefpodoxime proxetil on complexation with -cyclodextrin (P < 0.05) as compared to CPDX-PR alone. Amongst the complexes prepared by different methods, the complex prepared by freeze drying showed the highest dissolution rate (P< 0.01). The in vitro antimicrobial activity of cefpodoxime proxetil and its freeze dried complex (1:2) was studied against both antibiotic-susceptible and antibiotic-resistant clinical isolates of Neisseria gonorrhoeae. The freeze dried complex (1:2) inhibited all penicillin-susceptible strains and penicillinase-producing strains at 0.015 μg/ml concentration. Chromosomally resistant strains which were not responsive to penicillin were inhibited by the complex at 0.125 μg/ml concentration. The study revealed that complexation of cefpodoxime proxetil with -cyclodextrin effectively enhanced the aqueous solubility and in vitro antibacterial activity.

Coronavirus disease 2019 (COVID-19) has become a major challenge affecting almost every corner of the world, with more than five million deaths worldwide. Despite several efforts, no drug or vaccine has shown the potential to check the ever-mutating SARS-COV-2. The emergence of novel variants is a major concern increasing the need for the discovery of novel therapeutics for the management of this pandemic. Out of several potential drug targets such as S protein, human ACE2, TMPRSS2 (transmembrane protease serine 2), 3CLpro, RdRp, and PLpro (papain-like protease), RNA-dependent RNA polymerase (RdRP) is a vital enzyme for viral RNA replication in the mammalian host cell and is one of the legitimate targets for the development of therapeutics against this disease. In this study, we have performed structure-based virtual screening to identify potential hit compounds against RdRp using molecular docking of a commercially available small molecule library of structurally diverse and drug-like molecules. Since non-optimal ADME properties create hurdles in the clinical development of drugs, we performed detailed in silico ADMET prediction to facilitate the selection of compounds for further studies. The results from the ADMET study indicated that most of the hit compounds had optimal properties. Moreover, to explore the conformational dynamics of protein–ligand interaction, we have performed an atomistic molecular dynamics simulation which indicated a stable interaction throughout the simulation period. We believe that the current findings may assist in the discovery of drug candidates against SARS-CoV-2.

Background and Objective: The present study describes the UPLC-MS/MS method validation for the analysis of ornidazole in solid dispersion. Methods: The proposed UPLC-MS/MS method utilizes BEH Shield RP18 column (2.1 mm 100 mm, 1.7 μm) with a gradient programmed mobile phase composed of water and acetonitrile at a flow rate of 0.4 mL/min which varies with time program. Ornidazole was detected by UPLC-MS/MS with three proton adducts at m/z 82.04, 128.05 as daughter ions and 220.03 as a parent ion in Multiple Reaction Monitoring (MRM) operated in positive mode. Results: Adducts at m/z 128.05 was found to be the most stable and showed higher intensity was selected for quantification of ornidaozle in solid dispersion. In the method, validation linearity was determined at concentration range of 10-100ng/mL and a correlation coefficient was found (r2) ≥0.9994. The limit of detection and limit of quantification were found to be 1.5 and 4 ng/mL, respectively. Inter and Intra-day precision was found within 0.33 and 0.11% and accuracy within 100.08% and 100.04%. Conclusion: A sensitive and selective UPLC-MS/MS method had been validated for the analysis of ornidazole in solid dispersion. The proposed method of analysis of ornidazole in solid dispersion can be used in quality control laboratories.