Abstracts

Rationale: The therapeutic equivalence of FDA approved generics, including lamotrigine, has been questioned by neurologists and patients with epilepsy. A potential contributor to such concerns is pharmaceutical quality. In the case of lamotrigine tablets, attributes of pharmaceutical quality include tablet appearance, presence of lamotrigine in the tablet at the correct dose and without excessive variability, lack of excessive impurities, and sufficiently rapid drug dissolution from tablet. Tablets with poor pharmaceutical quality can be expected to pose potential bioinequivalence. The objective was to assess the pharmaceutical quality of three lots of LAMICTAL 100mg tablets and three lots of Teva lamotrigine 100mg tablets. Methods: LAMICTAL and Teva tablets were selected since they represent the brand and the most commonly dispensed lamotrigine generic, respectively. Three different lots of each brand and generic tablets were purchased commercially. The following pharmaceutical quality tests were performed: appearance, identity, assay, impurity, uniformity of dosage units, disintegration, dissolution (only lots A and D), friability, and loss on drying. Identity, assay, impurity, uniformity of dosage units, and dissolution were performed as specified in the USP monograph for lamotrigine tablets. Passing criteria for each test, except disintegration and loss on drying, were identified prior to testing. Results: Each lot passed each test. Assay results of LAMICTAL lots A, B, and C and Teva lots D, E, and F were 98.9%, 94.1%, 97.3%, 97.3%, 100.0%, and 96.3%, respectively. From impurity testing, lamotrigine related compound B in LAMICTAL lots A, B, and C and Teva lots D, E, and F were 0.05%, 0.05%, 0.05%, 0.02%, 0.03%, and 0.02%, respectively. Lamotrigine related compound C in LAMICTAL lots A, B, and C and Teva lots D, E, and F were 0.00%, 0.08%, 0.03%, 0.02%, 0.04%, and 0.05%, respectively. No individual unspecified impurity exceeded 0.2%. Total impurities in LAMICTAL lots A, B, and C and Teva lots D, E, and F were 0.16%, 0.33%, 0.16%, 0.28%, 0.27%, and 0.39%, respectively. Regarding uniformity of dosage units, the %CV from tablet weight variation for LAMICTAL lots A, B, and C and Teva lots D, E, and F were 1.48%, 1.15%, 2.65%, 1.01%, 0.67%, and 1.46%, respectively. Dissolution at 5 min of lot A and D was 93.2% and 100.9%, respectively. Dissolution at 10 and 15 min of lot A was 96.1% and 99.6%, respectively. Disintegration from LAMICTAL lots A, B, and C and Teva lots D, E, and F were 21s, 19s, 16s, 61s, 83s, and 75s, respectively. Friability results from LAMICTAL lots A, B, and C and Teva lots D, E, and F were 0.001%, 0.004%, 0.005%, 0.006%, 0.003%, and 0.008%, respectively. Loss on drying results from LAMICTAL lots A, B, and C and Teva lots D, E, and F were 4.34%, 3.36%, 3.48%, 3.61%, 3.47%, and 2.85%, respectively. Conclusions: LAMICTAL and Teva generic lamotrigine 100mg tablets showed acceptable pharmaceutical quality.