Gastroretentive raft liquid delivery system as a new approach to release extension for carrier-mediated drug

摘要

Gabapentin (GBP), an antiepileptic and anti-neuropathic agent, suffers from short half-life (5–7 h), has narrow absorption window, and is absorbed via carrier-mediated mechanism resulting in frequent dosing, poor compliance, and poor bioavailability (<60%). Moreover, GBP is a freely water-soluble drug, thus it is considered a challenging candidate to be formulated as extended release dosage form. In this study, raft forming systems were investigated as a potential drug delivery system for prolonging gastric residence time of GBP. A 2³ full factorial design was adopted to study the effect of formulation variables (% gellan gum, % GMO, and % LM-pectin 101), on the percent of GBP released at different time intervals (1, 5, and 8 h) as well as the gel strength, and thus was achieved an optimized formula with zero-order release profile suitable for once-daily administration. In vivo assessment was performed in rats to evaluate gastric residence of the gel formed. In addition, the oral bioavailability of GBP relative to commercially available Neurontin^® immediate release oral solution was also investigated. Significant increase was observed for Cmax, AUC(0–t), and AUC(0–∞). The increase in relative bioavailability of GBP from the optimized formula was 1.7 folds.