Abstract
Lacosamide (LCM) is a third-generation antiepileptic drug. Selective action of the drug on voltage-gated sodium channels reduces side effects. Oral administration of LCM shows good pharmacokinetic profile. However, the bitter taste of LCM is a barrier to the development of oral formulations. In this study, we aimed to prepare encapsulated LCM microparticles (MPs) for masking its bitter taste. Encapsulated LCM MPs were prepared with Eudragit® E100 (E100), a pH-dependent polymer, by spray drying. Three formulations comprising different ratios of LCM and E100 (3:1, 1:1, and 1:3) were prepared. Physicochemical tests showed that LCM was in an amorphous state in the prepared formulations, and they were not miscible. LCM-E100 (1:3) had a rough surface due to surface enrichment of LCM. Increased E100 ratio in LCM-E100 MPs resulted in better taste-making effectiveness: LCM-E100 (1:1) and LCM-E100 (1:3) showed good taste-masking effectiveness, while LCM-E100 (3:1) could not mask the bitter taste of LCM. Dissolution results of the prepared formulations showed good correlation with taste-masking effectiveness. Nevertheless, high E100 ratio reduced the stability of the prepared formulations. Especially the difference in initial dissolution profile observed for LCM-E100 (1:3) indicated rapid reduction in taste-masking effectiveness and surface recrystallization. Therefore, LCM-E100 formulation in the ratio of 1:1 was selected as the best formulation with good taste-masking effectiveness and stability.
Highlights
Epilepsy is a chronic neurological disorder of the brain which is recurrent and unpredictable [1], and is one of the most common neurological diseases worldwide.Lacosamide (LCM; [R]-2-acetamido-N-benzyl-3-methoxypropionamide) is a third-generation antiepileptic drug approved by the Food and Drug Administration in 2008 as an adjunctive therapy for partial onset seizures in patients with epilepsy aged ≥17 years in the United states
LCM-E100 (3:1), LCM-E100 (1:1), and LCM-E100 (1:3) MPs were prepared by spray drying
The entrapment efficiency of MPs was almost 100%, indicating that LCM and E100 were properly distributed in the droplets
Summary
Lacosamide (LCM; [R]-2-acetamido-N-benzyl-3-methoxypropionamide) is a third-generation antiepileptic drug approved by the Food and Drug Administration in 2008 as an adjunctive therapy for partial onset seizures in patients with epilepsy aged ≥17 years in the United states. Materials 2019, 12, 1000 voltage-gated sodium channels (VGSC) by selectively enhancing slow inactivation. VGSC blocking agents promote fast inactivation and block recovery from fast inactivation without any effect on slow inactivation [3,4]. The selective property of LCM stabilizes hyperexcitable neuronal membranes, inhibits neuronal firing, and reduces long-term channel availability without affecting other physiological functions such as cognitive deterioration [5]. Post-oral dose of LCM shows good pharmacokinetic properties, namely low protein binding capacity (
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