TY - JOUR
T1 - Lamotrigine therapy in patients after bariatric surgery
T2 - Potentially hampered solubility and dissolution
AU - Porat, Daniel
AU - Azran, Carmil
AU - Mualem, Yoni
AU - Vainer, Ella
AU - Gibori, Roni
AU - Vaynshtein, Julie
AU - Dukhno, Oleg
AU - Dahan, Arik
N1 - Copyright © 2021. Published by Elsevier B.V.
PY - 2021/11/15
Y1 - 2021/11/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85121099160&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ijpharm.2021.121298
DO - https://doi.org/10.1016/j.ijpharm.2021.121298
M3 - مقالة
C2 - 34793937
SN - 0378-5173
VL - 612
SP - 121298
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 121298
ER -
