How to reduce the treatment gap for people with epilepsy in resource-limited settings by innovative galenic formulations: A review of the current situation, overview of potential techniques, interests and limits.

Abstract : Epilepsy is a chronic neurological disease affecting more than 69 million people worldwide, nearly 90% of them in low and middle-income countries (LMICs). In those countries, only four major antiepileptic drugs are commonly used: phenobarbital, carbamazepine, sodium valproate and phenytoin. There are also problems with the accessibility, availability and quality of drugs. The main objective was to review the literature concerning "long" sustained-release formulations of AEDs that have the potential to reduce the number of administrations and help overcome problems of compliance, accessibility and the treatment gap. The main endpoint was a releasing of the active ingredient over more than 24h. We also assessed the feasibility and acceptability in resource-limited settings. Two drugs were found in unconventional release formulations: carbamazepine and sodium valproate; but they were not "long" sustained release because they required administration once a day. Several techniques were available, including: esterification, transdermal devices, liposomes and polymeric devices preformed or formed in situ. In situ methods for the preparation of injectable biodegradable microparticles or implants for controlled delivery seemed best suited to the objective. Furthermore, they appear to fulfil the requirements of feasibility and cost. Sodium valproate appeared as well to be a relevant candidate for a "long" sustained release formulation that would improve access to medicines for people with epilepsy in resource-limited settings. .