Sustained release matrix tablet is a delivery system by which the drug can be delivered at a controlled rate for long period of time. The present study aims at formulation, evaluation and optimization of captopril matrix tablets. A 32 full factorial design was adopted and all 9 batches were prepared by wet granulation method. Prepared granules and tablets were evaluated for precompression and postcompression characteristics respectively. Check point analysis was applied to the observations and the formula of the tablet was optimized. Optimized formula, F6 showed zero order drug release kinetics for the time period of 24 hours i.e. 17.55% release at the end of 2 hours, 53.4% release at the end of 12 hours and 100.24% release at the end of 24 hours. The results revealed that concentration of matrix forming agent and solution of granulating agent significantly affected in vitro drug release profile.
A simple, linear gradient, rapid, precise and stability-indicating RP-UPLC method was developed for the determination of Cloxacillin Sodium in its bulk form and formulation. Ultra performance liquid chromatography, a most promising advancement in a world of chromatography, reduces analysis time, increases reliability through higher resolution, sensitivity and selectivity as well as used as an economic method due to reducing solvent consumption. A chromatographic separation of a drug as well as its degradants was achieved using Waters acquity BEH, 2.1 × 100 mm, 1.7 μm C18 column with gradient of mobile phase A: phosphate buffer, pH 6.8 and mobile phase B: methanol:acetonitrile (75:25). The drug and degradants were monitored at a detection wavelength of 225 nm with a flow rate of 0.35 mL/min and an injection volume of 10 µL. The temperature of the column and auto sampler compartments was at 30°C and 25°C ± 1°C, respectively. The retention time of the drug was ∼6.9 min. The resolution of the drug and degradant peak was >1.5 in all cases. Force degradation of CLOX SOD was carried under alkaline, acidic, oxidative, thermal, photo degradation conditions and it was analyzed by the proposed method. The drug degrades under alkaline, acidic and oxidative conditions but was stable in temperature and light. A developed method was validated as per ICH guidelines using validation parameters such as precision, linearity and range, limit of quantification, specificity, assay and robustness.
Inhibitors of the SARS-CoV-2 main protease (Mpro) such as nirmatrelvir (NTV) and ensitrelvir (ETV) have proven effective in reducing the severity of COVID-19, but the presence of resistance-conferring mutations in sequenced viral genomes raises concerns about future drug resistance. Second-generation oral drugs that retain function on these mutants are thus urgently needed. We hypothesized that the covalent HCV protease inhibitor boceprevir (BPV) could serve as the basis for orally bioavailable drugs that inhibit SARS-CoV-2 Mpro more tightly than existing drugs. Performing structure-guided modifications of BPV, we developed a picomolar-affinity inhibitor, ML2006a4, with antiviral activity, oral pharmacokinetics, and therapeutic efficacy similar or superior to NTV. A crucial feature of ML2006a4 is a novel derivatization of the ketoamide reactive group that improves cell permeability and oral bioavailability. Finally, ML2006a4 is less sensitive to several mutations that cause resistance to NTV or ETV and occur in the natural SARS-CoV-2 population. Thus, anticipatory drug design can preemptively address potential resistance mechanisms.
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