DEVELOPMENT OF CONTROLLED RELEASE SOLIDS DOSAGE FORM OF MELINJO SEED SCLEROTESTE ETHANOL EXTRACT (GNETUM GNEMON L.) AS A NATURAL ANTIHYPERURICEMIA CANDIDATE

• Main Author: Masruriati, Eni
• Format: Dissertations
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/79632
• Institution: Institut Teknologi Bandung

The development of commercially valuable medical raw materials is still lacking. Melinjo (Gnetum gnemon L) could be developed. Melinjo (Gnetum gnemon L) has antihyperuricemia, antioxidant, antibacterial, antidiabetic, skin whitening, and other medical effects. Short biological half-life and limited absorption are its oral preparation drawbacks. Hyperuricemia is still common, hence melinjo seed sclerotesta (Gnetum gnemon L) is used to treat it. This study uses a controlled release matrix approach to increase bioavailability and prolong the antihyperuricemia action of ethanol extract of melinjo seeds scleroteste. HPMC K100M polymer and eudragit RS PO regulate active compound release for optimal release. The controlled release solid dosage form of melinjo seed sclerotesta ethanol extract's physical properties, in vitro resveratrol release, pharmacokinetic parameters in healthy and hyperuricemic mice, antihyperuricemic activity in hyperuricemic mice, and stability are characterised. Solid dosage forms in the form of a particulate system are produced by wet granulation utilising an HPMC K100M-eudragit RS PO matrix mixture. In vitro release profile studies were carried out using a USP Apparatus 3 (reciprocating cylinder) dissolution tester at 10 dpm in 200 mL 0.1 N HCl at 37 ± 0.5 °C for 24 hours with a test sample weight of 750 mg. Aliquots were collected at time intervals of 0.25;1;2;3;5;8;24 hours. Testing of pharmacokinetic parameters and antihyperuricemia activity tests used male Rattus norvegicus (Wistar strain) animals weighing 200–300 g (8–9 weeks). Hyperuricemia induction in mice was carried out using potassium oxonate 250 mg/kg BW intraperitoneally and chicken liver extract 10 mL/kg BW orally. The in vivo experimental protocol was approved by the Dental Health Research Ethics Committee, Faculty of Dentistry, Airlangga University. Ethical Clearance Certificate Number 493/HRECC/FODM/VIII/2021. Research data were analyzed using the IMB SPSS version 25 statistical computer program. Analysis Determination of resveratrol levels as a marker was carried out using KCKT Knauer German. Column C-8 (4.6 mm x 250 mm x 5µm, Reliant: Ireland). The analytical conditions were as follows: the mobile phase was an acetonitrile–water mixture (45:55, v/v), the flow rate was 1 mL/min, the detection wavelength was set at 280 nm, and the injection volume was 100 ?L. The extract contained flavonoids, phenols, steroids/triterpenoids, and saponins after phytochemical screening. The extract has 1.176% resveratrol and 2.45 ± 0.04 total phenol (g GAE/100 g). The flow rate (g/dt), water content (%), angle of repose (o), Carr index (%), and Haussner ratio of solid preparations containing melinjo seed sclerotesta ethanol extract match applicable standards and there are no major formula discrepancies. that it doesn't disrupt the following process. Test uniformity meets standards. Formula F3 with HPMC K100M-eudragit RS PO (75:25) releases resveratrol longer than extract and formula without matrix (F1). F3 released via Korsmeyer-Peppas kinetics. Drug elimination decreased, biological half-life increased, and AUC values increased on controlled release solid dosage forms (F3). Antihyperuricemia activity improved in controlled release formula. Stability of F3 follows a first-order reaction with t1/2 longer than F1 and extract.