Abstracts

Rationale: The therapeutic equivalence of generic and brand name antiepileptic drugs has been questioned by neurologists and the epilepsy community. A potential contributor to such concerns is pharmaceutical quality. The objective was to assess the biopharmaceutic risk of brand name Lamictal 100mg tablets and generic lamotrigine 100mg tablets from several manufacturers.Methods: Lamotrigine was characterized in terms of the Biopharmaceutics Classification System (BCS), including aqueous solubility and Caco-2 permeability. A panel of pharmaceutical quality tests was also performed on three batches of Lamictal, three batches of Teva generic, and one batch of each of four other generics: appearance, identity, assay, impurity, uniformity of dosage units, disintegration, dissolution, friability, and loss on drying.Results: These market surveillance results indicate that all brand name and generic lamotrigine 100mg tablets passed all tests and showed acceptable pharmaceutical quality and low biopharmaceutic risk. Lamotrigine was classified as a BCS class IIb drug, exhibiting pH dependent aqueous solubility and dissolution. At pH 1.2 and 4.5, lamotrigine exhibited high solubility, whereas lamotrigine exhibited low solubility at pH 6.8, including non-sink dissolution. Lamotrigine showed high Caco-2 permeability. The apparent permeability (Papp) of lamotrigine was 73.7 ± 8.7 x 10-6 cm/sec in the apical to basolateral (AP-BL) direction and 41.4 ± 1.6 x 10-6 cm/sec in the BL-AP direction, which were higher than metoprolol’s AP-BL Papp of 21.2 ± 0.9 x 10-6 cm/sec and BL-AP Papp of 34.6 ± 4.6 x 10-6 cm/sec, respectively.Conclusions: Overall, lamotrigine’s favorable biopharmaceutics from a drug substance perspective and favorable quality characteristics from a tablet formulation perspective suggest multisource lamotrigine tablets to exhibit low biopharmaceutic risk.