Pharmacomagnetography of floating gastroretentive systems in vivo in different prandial states evaluated by AC biosusceptometry.

In recent decades, the development of effective therapies with minimal adverse effects has become a major challenge in the pharmaceutical field. Despite its popularity, oral administration faces limitations related to the physiological variability of the gastrointestinal tract (GIT), such as gastric emptying time, absorption window, and site of drug release. In this context, modified-release systems-especially gastroretentive drug delivery systems (GRDDS)-have gained prominence. GRDDS aim to prolong gastric retention time (GRT), facilitating controlled and localized drug release, particularly beneficial for drugs with limited absorption windows or instability in alkaline pH. This study evaluated the in vivo performance of a magnetic floating drug delivery system (MFDDS) containing metronidazole using pharmacomagnetography based on alternating current biosusceptometry (ACB) in healthy volunteers (n = 12, aged 19-21 years) under fasted and fed conditions. Results demonstrated that the prandial state significantly influenced MFDDS behavior, with food intake prolonging both the floating lag time (FLT) (105-120 min fed vs. 45-60 min fasted) and gastric retention time (GRT) (165.0±32.2 min fed vs. 118.3±35.3 min fasted, p < 0.0001). The orocecal transit time (OCTT) was similar between groups (271.7±32.0 min fed vs. 254.2±44.9 min fasted, p > 0.05), while small intestine transit time (SITT) was shorter in the fed state (111.7±22.3 min) compared to the fasted state (140.0±47.7 min), though not statistically significant. Pharmacokinetic parameters showed significant differences, with the fed state resulting in delayed time to maximum concentration (Tmax) (252.0±52.9 min fed vs. 174.0±60.0 min fasted, p < 0.05) but substantially higher maximum plasma concentrations (Cmax) (11.0±5.7 µg/mL fed vs. 4.7±2.2 µg/mL fasted, p < 0.05) and area under the curve (AUC360) (2606.1±1825.5 µg·h/mL fed vs. 969.3±638.3 µg·h/mL fasted, p < 0.05). The time lag before detectable plasma concentration (Tlag) was similar between groups (67.5±21.8 min fed vs. 86.7±31.4 min fasted, p > 0.05). The increased viscosity of gastric contents in the fed state delayed the initial tablet flotation by forming a hydrophobic barrier around the tablet, restricting gastric fluid diffusion into the polymeric matrix. This extended gastric retention in the fed state resulted in more complete and sustained metronidazole absorption, confirming the effectiveness of the gastroretentive system in optimizing drug bioavailability, particularly when administered after meals.