期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 612, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2021.121298
关键词
Metabolic surgery; Mini-gastric bypass; Lamotrigine; Solubility; dissolution; Basic drugs; Gastric content
Bariatric surgery can affect the oral exposure of drugs, especially marginally soluble weak bases like lamotrigine. Research found that post-surgery gastric conditions led to decreased solubility of lamotrigine, impacting the dissolution of higher dose tablets in particular. Close monitoring of drug absorption is recommended after bariatric surgery based on these findings.
Bariatric surgery is an effective treatment of obesity and related comorbidities. With surgery, the stomach undergoes major anatomical/physiological changes that may affect the oral exposure of drugs, especially marginally soluble weak bases, such as lamotrigine. The aim of this work was to study the solubility/dissolution of lamotrigine in conditions simulating the stomach before vs. after bariatric surgery. Lamotrigine solubility was studied in-vitro, as well as ex-vivo in gastric content aspirated from patients before vs. after bariatric surgery. We then compared the dissolution kinetics of various marketed lamotrigine products in pre- vs. post-operative stomach conditions, different in volume, pH, agitation strength and speed. Decreased lamotrigine solubility with increasing pH (from 1.37 +/- 0.09 (pH = 1) to 0.22 +/- 0.03 mg/mL (pH = 7)) was obtained. Twelve-fold higher lamotrigine solubility was revealed in gastric content aspirated before vs. after surgery (8.5 +/- 0.7 and 0.7 +/- 0.01 mg/mL, respectively). Dissolution studies showed that only the lowest dose (25 mg) fully dissolved in the post-surgery stomach conditions, while at higher doses, lamotrigine tablet dissolution was impaired. Neither fast-dissolving tablet, nor tablet crushing, helped resolving this problem. Based on these results, and given that dissolution of the drug dose governs the subsequent absorption, close monitoring of this essential drug is advised after bariatric surgery.
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