Advancing Lamotrigine Therapy: Piezoelectric Atomized Cloud Drying-Developed Microparticles in Lyophilized Orally Disintegrating Tablets with Characterization and PBPK Simulation for Enhanced Dissolution, Rapid Absorption, and Faster Onset of Action

Collaborators GBDE. Global, regional, and National burden of epilepsy, 1990–2021: a systematic analysis for the global burden of disease study 2021. Lancet Public Health. 2025;10(3):e203–27. https://doi.org/10.1016/S2468-2667(24)00302-5.

Article  Google Scholar 

Olusanya BO, Wright SM, Nair MKC, Boo NY, Halpern R, Kuper H, et al. Global burden of childhood epilepsy, intellectual disability, and sensory impairments. Pediatrics. 2020. https://doi.org/10.1542/peds.2019-2623.

Article  PubMed  Google Scholar 

Collaborators GBDE. Global, regional, and national burden of epilepsy, 1990–2016: a systematic analysis for the global burden of disease study 2016. Lancet Neurol. 2019;18(4):357–75. https://doi.org/10.1016/S1474-4422(18)30454-X.

Article  Google Scholar 

Zhang YJ, Kong XM, Lv JJ, Yang CH, Li XY, Yang XT, et al. Analysis of the global burden of disease study highlights the global, regional, and national trends of idiopathic epilepsy epidemiology from 1990 to 2019. Prev Med Rep. 2023;36: 102522. https://doi.org/10.1016/j.pmedr.2023.102522.

Article  PubMed  PubMed Central  Google Scholar 

de Boer HM, Mula M, Sander JW. The global burden and stigma of epilepsy. Epilepsy Behav. 2008;12(4):540–6. https://doi.org/10.1016/j.yebeh.2007.12.019.

Article  PubMed  Google Scholar 

Singh G, Sander JW. The global burden of epilepsy report: implications for low- and middle-income countries. Epilepsy Behav. 2020;105: 106949. https://doi.org/10.1016/j.yebeh.2020.106949.

Article  PubMed  Google Scholar 

Tu L, Xiao J, Hong Q, Ouyang A, Tu Y, Wang S. Assessment of adverse events of the novel antiepileptic drug lamotrigine: a real-world pharmacovigilance study based on FAERS. Expert Opin Drug Saf. 2025. https://doi.org/10.1080/14740338.2025.2465867.

Article  PubMed  Google Scholar 

Alabi A, Todd A, Husband A, Reilly J. Safety profile of lamotrigine in overdose. Ther Adv Psychopharmacol. 2016;6(6):369–81. https://doi.org/10.1177/2045125316656707.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Valencia I, Pinol-Ripoll G, Khurana DS, Hardison HH, Kothare SV, Melvin JJ, et al. Efficacy and safety of lamotrigine monotherapy in children and adolescents with epilepsy. Eur J Paediatr Neurol. 2009;13(2):141–5. https://doi.org/10.1016/j.ejpn.2008.03.002.

Article  PubMed  Google Scholar 

Yu X, Li J, Wu C, Yang D, Li L, Lu Y, et al. Exploring the solubility of novel lamotrigine drug–drug salts: the role of pH and structural variability. CrystEngComm. 2025;27(6):820–32. https://doi.org/10.1039/d4ce01111b.

Article  CAS  Google Scholar 

Salamah M, Sipos B, Schelz Z, Zupko I, Kiricsi A, Szalenko-Tokes A, et al. Development, in vitro and ex vivo characterization of lamotrigine-loaded bovine serum albumin nanoparticles using QbD approach. Drug Deliv. 2025;32(1):2460693. https://doi.org/10.1080/10717544.2025.2460693.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Neerumalla S, Chhowala I, Patel M. Formulation design of oral lamotrigine suspension for the treatment of epilepsy. Curr Med Res Pract. 2022;12(4):157–61. https://doi.org/10.4103/cmrp.cmrp_45_22.

Article  Google Scholar 

Hashimoto Y, Kotake K, Watanabe N, Fujiwara T, Sakamoto S. Lamotrigine in the maintenance treatment of bipolar disorder. Cochrane Database Syst Rev. 2021;9(9): CD013575. https://doi.org/10.1002/14651858.CD013575.pub2.

Article  PubMed  Google Scholar 

Haenen N, Kamperman AM, Prodan A, Nolen WA, Boks MP, Wesseloo R. The efficacy of lamotrigine in bipolar disorder: a systematic review and meta-analysis. Bipolar Disord. 2024;26(5):431–41. https://doi.org/10.1111/bdi.13452.

Article  CAS  PubMed  Google Scholar 

Naguy A, Al-Enezi N. Lamotrigine uses in psychiatric practice. Am J Ther. 2019;26(1):e96–102. https://doi.org/10.1097/MJT.0000000000000535.

Article  PubMed  Google Scholar 

Steinbaugh L, Szaflarski JP. Adjunctive therapy for the treatment of primary generalized tonic-clonic seizures: focus on once-daily lamotrigine. Drug Des Devel Ther. 2010;4:337–42. https://doi.org/10.2147/DDDT.S11175.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cerulli Irelli E, Cocchi E, Morano A, Gesche J, Caraballo RH, Lattanzi S, et al. Levetiracetam vs lamotrigine as first-line antiseizure medication in female patients with idiopathic generalized epilepsy. JAMA Neurol. 2023;80(11):1174–81. https://doi.org/10.1001/jamaneurol.2023.3400.

Article  PubMed  PubMed Central  Google Scholar 

Betchel NT, Fariba KA, Saadabadi A. Lamotrigine. StatPearls. Treasure Island (FL): StatPearls publishing copyright © 2025. StatPearls Publishing LLC.; 2025.

Brigo F, Jones K, Eltze C, Matricardi S. Anti-seizure medications for Lennox-Gastaut syndrome. Cochrane Database Syst Rev. 2021;4(4): CD003277. https://doi.org/10.1002/14651858.CD003277.pub4.

Article  PubMed  Google Scholar 

Tjia-Leong E, Leong K, Marson AG. Lamotrigine adjunctive therapy for refractory generalized tonic-clonic seizures. Cochrane Database Syst Rev. 2010;12CD007783. https://doi.org/10.1002/14651858.CD007783.pub2.

Vaithianathan S, Raman S, Jiang W, Ting TY, Kane MA, Polli JE. Biopharmaceutic risk assessment of brand and generic lamotrigine tablets. Mol Pharm. 2015;12(7):2436–43. https://doi.org/10.1021/acs.molpharmaceut.5b00154.

Article  CAS  PubMed  Google Scholar 

Abdelmonem R, Azer MS, Makky A, Zaghloul A, El-Nabarawi M, Nada A. Development, characterization, and in-vivo pharmacokinetic study of lamotrigine solid self-nanoemulsifying drug delivery system. Drug Des Devel Ther. 2020. https://doi.org/10.2147/DDDT.S263898.

Article  PubMed  PubMed Central  Google Scholar 

Lakshmi P, Reddy S, Kishore C, Reddy S. Formulation and evaluation of oral disintegrating tablets of lamotrigine solid dispersions: oral dispersible tablets. Iran J Pharm Sci. 2013;9(1):1–12.

CAS  Google Scholar 

Rambeck B, Wolf P. Lamotrigine clinical pharmacokinetics. Clin Pharmacokinet. 1993;25(6):433–43. https://doi.org/10.2165/00003088-199325060-00003.

Article  CAS  PubMed  Google Scholar 

Polepally AR, Remmel RP, Brundage RC, Leppik IE, Rarick JO, Ramsay RE, et al. Steady-state pharmacokinetics and bioavailability of immediate-release and extended-release formulations of lamotrigine in elderly epilepsy patients: use of stable isotope methodology. J Clin Pharmacol. 2015;55(10):1101–8. https://doi.org/10.1002/jcph.522.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li Y, Zhang F, Xu Y, Hu J, Li H. Pharmacokinetics. Safety, and tolerability of lamotrigine chewable/dispersible tablet following repeat-dose administration in healthy Chinese volunteers. Clin Pharmacol Drug Dev. 2018;7(6):627–33. https://doi.org/10.1002/cpdd.449.

Article  CAS  PubMed  Google Scholar 

Betchel NT, Fariba KA, Lamotrigine AS. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025.

Google Scholar 

Morris RG, Black AB, Harris AL, Batty AB, Sallustio BC. Lamotrigine and therapeutic drug monitoring: retrospective survey following the introduction of a routine service. Br J Clin Pharmacol. 1998;46(6):547–51. https://doi.org/10.1046/j.1365-2125.1998.00835.x.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sharma C, Dubey R, Kumar H, Saha N. Food reduces the bioavailability of lamotrigine. Indian J Med Res. 2005;121(5):659–64.

CAS  PubMed  Google Scholar 

Kande KV, Kotak DJ, Degani MS, Kirsanov D, Legin A, Devarajan PV. Microwave-assisted development of orally disintegrating tablets by direct compression. AAPS PharmSciTech. 2017;18(6):2055–66. https://doi.org/10.1208/s12249-016-0683-z.

Article  CAS  PubMed  Google Scholar 

Wangemann M, Retzow A, Pohlmann-Eden B. In vivo biopharmaceutical characterisation of a new formulation containing the antiepileptic drug lamotrigine in comparison to plain and dispersible/chewable lamotrigine tablets. Arzneimittelforschung. 2005;55(6):307–11. https://doi.org/10.1055/s-0031-1296864.

Article  CAS  PubMed  Google Scholar 

Loscertales HR, Modamio P, Lastra CF, Marino EL. Assessing the stability of lamotrigine dispersible/chewable tablets when stored in blister punch cards. Curr Med Res Opin. 2017;33(5):949–53. https://doi.org/10.1080/03007995.2017.1297927.

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