SeDeM-Assisted Formulation of Lamotrigine Orally Disintegrating Minitablets for Pediatric Epilepsy: In Vitro and In Vivo Assessment

Abstract

Purpose

Lamotrigine therapy in pediatric epilepsy is constrained by the absence of age-appropriate dosage forms, as commercially available tablets (25–200 mg) are difficult to swallow, often require splitting, and may result in inaccurate dosing and poor adherence. This study aimed to develop pediatric-friendly orally disintegrating minitablets (ODMTs) of Lamotrigine using the SeDeM expert system and co-processed excipients to improve manufacturability, dose accuracy, and oral bioavailability.

Methods

SeDeM expert analysis was employed to evaluate the flowability and compressibility of Lamotrigine and six co-processed excipients. ODMTs were prepared by direct compression and characterized for weight variation, hardness, friability, wetting time, disintegration time, and in vitro drug release. The optimized formulation was further evaluated by pharmacokinetic studies in rabbits.

Results

SeDeM analysis demonstrated poor flow and compressibility of Lamotrigine, with an incidence of good compressibility (IGC) value of 3.568, indicating unsuitability for direct compression. Among the evaluated excipients, PHARMABURST™ 500 exhibited superior flow (PI = 0.833) and compressibility (IGC = 6.10). The optimized formulation showed uniform weight (24.5 ± 0.64 mg), hardness (2.5 ± 0.06 kg/cm²), friability below 1%, rapid wetting (6 s), fast disintegration (10 s), and 98.88% drug release within 25 min. Pharmacokinetic studies demonstrated enhanced bioavailability with a 2.1-fold increase in AUC, higher C_max (93.69 µg/mL), and reduced T_max (1 h).

Conclusion

SeDeM-guided formulation using PHARMABURST™ 500 successfully produced stable, rapidly disintegrating Lamotrigine ODMTs with improved manufacturability, dissolution performance, and bioavailability, representing a promising pediatric dosage form for epilepsy management.

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Mali, K.D., Pardeshi, C.V. SeDeM-Assisted Formulation of Lamotrigine Orally Disintegrating Minitablets for Pediatric Epilepsy: In Vitro and In Vivo Assessment. J Pharm Innov 22, 112 (2027). https://doi.org/10.1007/s12247-026-10987-z