The objective of the present study was to develop once-daily sustained-release matrix tablets of nicorandil, a novel potassium channel opener used in cardiovascular diseases. The tablets were prepared by the wet granulation method. Ethanolic solutions of ethylcellulose (EC), Eudragit RL-100, Eudragit RS-100, and polyvinylpyrrolidone were used as granulating agents along with hydrophilic matrix materials like hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose, and sodium alginate. The granules were evaluated for angle of repose, bulk density, compressibility index, total porosity, and drug content. The tablets were subjected to thickness, diameter, weight variation test, drug content, hardness, friability, and in vitro release studies. The granules showed satisfactory flow properties, compressibility, and drug content. All the tablet formulations showed acceptable pharmacotechnical properties and complied with in-house specifications for tested parameters. According to the theoretical release profile calculation, a once-daily sustained-release formulation should release 5.92 mg of nicorandil in 1 hour, like conventional tablets, and 3.21 mg per hour up to 24 hours. The results of dissolution studies indicated that formulation F-I (drug-to-HPMC, 1:4; ethanol as granulating agent) could extend the drug release up to 24 hours. In the further formulation development process, F-IX (drug-to-HPMC, 1:4; EC 4% wt/vol as granulating agent), the most successful formulation of the study, exhibited satisfactory drug release in the initial hours, and the total release pattern was very close to the theoretical release profile. All the formulations (except F-IX) exhibited diffusion-dominated drug release. The mechanism of drug release from F-IX was diffusion coupled with erosion.

The objective of this prospective observational study was to assess the clinical significance of neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR) and lymphocyte–monocyte ratio (LMR) as potential biomarkers to identify post-PNL SIRS or sepsis. Demographic data and laboratory data including hemoglobin (Hb), total leucocyte count (TLC), serum creatinine, urine microscopy and culture were collected. The NLR, LMR and PLR were calculated by the mathematical division of their absolute values derived from routine complete blood counts from peripheral blood samples. Stone factors were assessed by non-contrast computerized tomography of kidneys, ureter and bladder (NCCT KUB) and included stone burden (Volume = L × W × D × π × 0.167), location and Hounsfield value and laterality. Intraoperative factors assessed were puncture site, tract size, tract number, operative time, the need for blood transfusion and stone clearance. Of 517 patients evaluated, 56 (10.8%) developed SIRS and 8 (1.5%) developed sepsis. Patients developing SIRS had significantly higher TLC (10.4 ± 3.5 vs 8.6 ± 2.6, OR 1.19, 95% CI 1.09–1.3, p = 0.000002), higher NLR (3.6 ± 2.4 vs 2.5 ± 1.04, OR 1.3, 95% CI = 1.09–1.5, p = 0.0000001), higher PLR (129.3 ± 53.8 vs 115.4 ± 68.9, OR 1.005, 95% CI 1.001–1.008, p = 0.005) and lower LMR (2.5 ± 1.7 vs 3.2 ± 1.8, OR 1.18, 95% CI 1.04–1.34, p = 0.006). Staghorn stones (12.8 vs 3.24%, OR 4.361, 95% CI 1.605–11.846, p = 0.008) and long operative times (59.6 ± 14.01 vs 55.2 ± 16.02, OR 1.01, 95% CI 1.00–1.03, p = 0.05) had significant association with postoperative SIRS. In conclusion, NLR, PLR and LMR can be useful independent, easily accessible and cost-effective predictors for early identification of post-PNL SIRS/sepsis.

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