FORMULASI DAN EVALUASI SEDIAAN MULTIUNIT G.4STRORETENTIVE METFOTMIN HCL DENGAN TEKNIK PEMBENTUKAN GAS

• Main Author: Christy, Gabriela
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/64297
• Institution: Institut Teknologi Bandung

Metformin hydrochloride (HCI) is the first choice drug used in the treatment of type IT Diabetes Mellitus (Non Insulin Dependent Diabetes Mellitus). It has a Narrow Absorption Window (NAW) characteristic, and the main absorption site is in the stomach and upper intestine. The limited and variance of gastric residence time lead to a slow and incomplete absorption of metformin 1-1C1, and also a fluctuation of its plasma concentration. Metformin HC1 also has a relatively short elimination half life (0.9-2.6 hours). Therefore, the frequent dosing schedule is needed to maintain its effective concentration in the systemic circulation over an extended period of time. To overcome these problems, metformin HCI was formulated into a gastroretentive multiunit dosage form that achieved by gas formation technique. This dosage form also facilitated a sustained release system. The core pellet containing metformin HCI, Avicel PH. 101, and PVP K-25 was first prepared by extrusion¬spheronization method, continued with coating process by fluidized bed drying method. The aim of this coating process was to cover the core pellet with inner sustained release layer, middle gas formation layer, and outer gas entrapment layer, respectively. The evaluations were done for the coated pellet, including physical evaluation (organoleptic, size distribution, morphology, flow ability, bulk density and friability), drug content assay and weight gain, floating ability on pH 1.2 HO solution, and also the in vitro drug release profile. The core pellet that was used for coating contained 38.64 ± 0.06 mg of metformin HCI per 100 mg pellet. The evaluation study demonstrated that formula with a combination of Eudragit RS PO and cetyl alcohol as the inner sustained release layer, sodium bicarbonate and FIPMC as the middle gas formation layer, and combination of Eudragit RS PO-RL PO (25:75) as the outer gas entrapment layer showed the best gastroretentive system. This formula contained 18.68 f 0,10 mg metformin HCI per 100 mg coated pellet, with a desirable floating lag time (<30 s) and 81.10 ± 1.90% pellet was remained floating until 8 hours. The in vitro drug release study also revealed that this formula showed the best sustained release system, with 68.16 + 0.40% of metformin HCI released after 8 hours. Thus, the developed formula enabled to prolong the drug retainment for 8 hours in the stomach with quasi-Fickian controlled diffusion release mechanism.