The study of technological properties and biopharmaceutical solubility of phenyltetrahydroquinolinedione derivative with TRPA1-antagonistic activity

Introduction. In accordance with the principles described in ICH Q8 guideline, the critical characteristics of the components of a dosage form that can affect its quality should be studied before the serial production of a drug. Such parameters include technological properties and biopharmaceutical solubility of an active pharmaceutical ingredient. Objective: to investigate the technological properties and biopharmaceutical solubility of the original substance of a phenyltetrahydroquinolinedione derivative – TRPA1 antagonist in order to develop a solid dosage form based on it. Material and methods. Flowability and angle of repose were determined using an Erweka GTL flow tester. The bulk volume before and after compaction was determined using an ETD-1020 bulk density tester. Equilibrium biopharmaceutical solubility was determined using dissolution tester DT 626/1000 HH. The dissolved quantity of the substance was determined using Agilent 8453 UV spectrophotometer. Results. The flowability was 18.68±1.15 g/s (25 mm funnel); the angle of repose was 46.37±2.04°, the compressibility index and the Hausner ratio were 31.83±1,33% and 1.47±0,09 units, respectively. The calculated therapeutic dose did not completely dissolve in 250 ml of the medium at any pH value. The biopharmaceutical solubility at pH 1.2 was 26.64±1.36 µg/ml, at pH 4.5 – 2.72±0.15 µg/ml, at pH 6.8 – 3.8±0.21 µg/ml. Conclusion. According to the results the following conclusions can be made: it is necessary to use the granulation method or to use the excipients for direct compression; the dissolution profile of the substance allows us to attribute it to class II or IV of the biopharmaceutical classification system, so the development of the dosage form of this substance should be aimed at increasing its solubility or solubility and permeability.