Vaithianathan Soundarya, Raman Siddarth, Jiang Wenlei, Ting Tricia Y, Kane Maureen A, Polli James E
†Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland 21201, United States.
‡Food and Drug Administration, Rockville, Maryland 20852, United States.
Mol Pharm. 2015 Jul 6;12(7):2436-43. doi: 10.1021/acs.molpharmaceut.5b00154. Epub 2015 Jun 2.
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 100 mg tablets and generic lamotrigine 100 mg tablets from several manufacturers. 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. These market surveillance results indicate that all brand name and generic lamotrigine 100 mg 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) × 10(-6) cm/s in the apical-to-basolateral (AP-BL) direction and (41.4 ± 1.6) × 10(-6) cm/s in the BL-AP direction, which were higher than metoprolol's AP-BL Papp of (21.2 ± 0.9) × 10(-6) cm/s and BL-AP Papp of (34.6 ± 4.6) × 10(-6) cm/s. Overall, lamotrigine's favorable biopharmaceutics from a drug substance perspective and favorable quality characteristics from a tablet formulation perspective suggest that multisource lamotrigine tablets exhibit a low biopharmaceutic risk.
通用名和品牌名抗癫痫药物的治疗等效性受到了神经科医生和癫痫学界的质疑。引发此类担忧的一个潜在因素是药品质量。目的是评估来自多家制造商的品牌名拉莫三嗪100毫克片剂和通用名拉莫三嗪100毫克片剂的生物药剂学风险。根据生物药剂学分类系统（BCS）对拉莫三嗪进行了表征，包括水溶性和Caco-2通透性。还对三批品牌名拉莫三嗪、三批梯瓦通用名产品以及其他四个通用名产品各一批进行了一组药品质量测试：外观、鉴别、含量测定、杂质、剂量单位均匀度、崩解、溶出、脆碎度和干燥失重。这些市场监测结果表明，所有品牌名和通用名拉莫三嗪100毫克片剂均通过了所有测试，显示出可接受的药品质量和低生物药剂学风险。拉莫三嗪被归类为BCS IIb类药物，表现出pH依赖性水溶性和溶出度。在pH 1.2和4.5时，拉莫三嗪具有高溶解度，而在pH 6.8时拉莫三嗪溶解度低，包括非漏槽溶出。拉莫三嗪显示出高Caco-2通透性。拉莫三嗪在顶侧到基底外侧（AP-BL）方向的表观渗透率（Papp）为(73.7 ± 8.7) × 10(-6) cm/s，在基底外侧到顶侧（BL-AP）方向为(41.4 ± 1.6) × 10(-6) cm/s，高于美托洛尔在AP-BL方向的Papp (21.2 ± 0.9) × 10(-6) cm/s和在BL-AP方向的Papp (34.6 ± 4.6) × 10(-6) cm/s。总体而言，从原料药角度看拉莫三嗪良好的生物药剂学性质以及从片剂制剂角度看良好的质量特性表明，多来源拉莫三嗪片剂具有低生物药剂学风险。
