Abstract
Weak base drugs tend to precipitate in the intestine, leading to a decrease in their bioavailability. Precipitation initiates with supersaturation due to a pH shift from the stomach to the small intestine. Using natural polymers as precipitation inhibitors is still limited and has not yielded optimal results. This study aims to determine the potential of alginate, gum acacia, pectin, and carrageenan as inhibitors of ketoconazole precipitation. Ketoconazole beads were created using polymer combinations such as alginate-gum acacia (AG), alginate-pectin (AP), and alginate-carrageenan (AK) in ratios of 75:25 and 50:50. Supersaturation testing was performed on ketoconazole beads using the pH shift method with a 2-compartment model system transferred via a peristaltic pump. The most effective ketoconazole beads as precipitation inhibitors were tested in vivo on rabbits. The results of the supersaturation testing showed that AG75 beads were the most effective in inhibiting ketoconazole precipitation. The relative bioavailability of AG75 beads in comparison to pure ketoconazole was 185.34 % ± 34.17. The combination of natural polymers in the form of alginate and gum acacia, with a ratio of 75:25, has the potential to act as a precipitation inhibitor of ketoconazole, a weak base drug, thereby increasing its bioavailability.
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