| Abstract [eng] |
Master's thesis of Kevin Švedko's "Manufacturing of Solid Pharmaceutical Forms with Fisetin and Evaluation of Antioxidant". Scientific supervisor assistant Dr. Rasa Kalėdaitė; Vilnius University, Faculty of Medicine, Institute of Biomedical Sciences (Pharmaceutical Centre), Vilnius 2026. Aim of the study: Evaluate the antioxidant properties of fisetin using the DPPH method, develop solid pharmaceutical forms containing fisetin, assess and compare the quality characteristics of capsule and tablet as solid dosage forms. Objectives: 1. To determine the content of phenolic compounds in fisetin using the Folin–Ciocalteu method and to evaluate its antioxidant activity using the DPPH (2,2-diphenyl-1-picrylhydrazyl) method. 2. To select suitable excipients and a binder for the production of fisetin-containing granules and to manufacture solid pharmaceutical dosage forms (tablets and capsules). 3. To evaluate quality characteristics of manufactured tablets and capsules with fisetin by determining the average mass, friability, and disintegration time of tablets, as well as the average mass and disintegration time of fisetin capsules. Methods: Based on pharmacopeial methods (Carr index and Hausner ratio), the flow properties of dry fisetin extract and prepared granules were evaluated. Avicel® PH 102 was used as the main excipient, while Aerosil® 200 and magnesium stearate served as lubricants to improve flowability. Granules were produced by wet granulation using a 20% ethanolic povidone solution, and their composition was assessed by analytical sieving. Four batches of capsules and tablets containing fisetin extract were manufactured using a capsule-filling machine and a single punch tablet press. The quality of the dosage forms was evaluated according to European Pharmacopoeia requirements for uniformity of mass, disintegration, and friability. The phenolic content of the extract was determined in different ethanol solutions using the Folin–Ciocalteu method, and antioxidant activity was assessed by the DPPH method. Results and conclusions: FE and MKC (Avicel® PH 102) powders were fine and had poor flowability. Wet granulation using an ethanolic solution of povidone improved the flowability of the tableting mixture. The narrowest granule size distribution was found in the fourth (20 % FE and 80 % MKC) series, with almost 40 % (38.2 %) of the granules being 1.4–1 mm in diameter. The widest granule size distribution was found in the first (50 % FE and 50 % MKC) and second (60 % FE and 40 % MKC) granule series. The third (70 % FE and 30 % MKC) and fourth (80 % FE and 20 % MKC) batches of prepared capsules did not comply with the requirements of the European Pharmacopoeia regarding mass uniformity, as the maximum mass deviation exceeded 10 %. The maximum deviation reached 11.68% for the third batch and 14.55 % for the fourth batch. The second, third, and fourth batches of tablets also did not meet the European Pharmacopoeia requirements regarding mass uniformity, as the maximum mass deviation exceeded 5 %. The deviation was 8.42 % for the second batch, 9.23 % for the third batch, and 16.09 % for the fourth batch. In summary, based on the results of all conducted studies, it can be stated that capsule batches 1 and 2, as well as tablet batch 1, met all the investigated quality requirements. These batches complied with the requirements of the European Pharmacopoeia for mass uniformity, disintegration, and mechanical resistance, and therefore can be considered the most suitable for further development of pharmaceutical forms. Evaluation of the phenolic compound content and antioxidant activity of the fisetin extract revealed that the highest phenolic content and antioxidant activity were obtained using a 70 % ethanolic solution. |
