Design and Simulation of Lamotrigine Intermittent Release from a Subcutaneous Implant with an Enzymatic Biosensor Based on Clinical Data

Epilepsy can be effectively controlled with appropriately selected antiepileptic drugs and carefully titrated dosage regimens. Although lamotrigine exhibits favorable pharmacokinetic properties following oral administration, fluctuations in plasma concentration may still occur due to interindividual variability, irregular dosing, and pharmacokinetic interactions. In this study, a subcutaneous implant capable of monitoring plasma lamotrigine levels and adjusting drug delivery accordingly was developed to maintain stable therapeutic concentrations. The proposed system combines intermittent drug release with continuous concentration monitoring using an enzymatic biosensor. A pharmacokinetic model based on first-order absorption and elimination kinetics was implemented in MATLAB/Simulink using clinical lamotrigine concentration data obtained from patients receiving chronic therapy. In the closed-loop configuration, biosensor measurements were used as feedback for a proportional–integral (PI) controller that adjusted the implant release rate in real time. System performance was evaluated using in silico simulations. The open-loop system produced rapid concentration peaks (Cmax ≈ 0.06 mmol/L) followed by a decline below the therapeutic threshold within approximately 80 min. In contrast, the closed-loop system achieved lower peak concentrations (Cmax ≈ 0.045 mmol/L) and maintained plasma concentrations within the therapeutic range of 0.02–0.03 mmol/L with reduced fluctuations. These findings support further investigation of biosensor-guided closed-loop lamotrigine delivery systems.