Pharmaceutical composition and method for treating seizure disorders
Inventors
Plakogiannis, Fotios M. • Lather, Tamanna • Modi, Nisarg • Borovinskaya, Marina
Assignees
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Publication Number
US-12016829-B2
Publication Date
2024-06-25
Expiration Date
Abstract
The present disclosure relates to the transdermal administration of cannabidiol (CBD) for the reduction of seizure frequency in the treatment of “treatment-resistant epilepsy” (TRE).
Core Innovation
The invention relates to a transdermal pharmaceutical composition comprising synthetically produced cannabidiol as an active agent, formulated as a drug-in-adhesive transdermal patch. The composition is configured to provide an equivalent to an oral dose in a patient selected from specified oral-dose ranges while delivering the active agent at a constant rate of delivery over at least 7 days. The patch includes a silicon pressure sensitive adhesive, a suspending agent comprising silicon dioxide, a solvent comprising propylene glycol, a penetration enhancer comprising oleic acid, and an antioxidant comprising butylated hydroxytoluene (BHT).
The invention further provides the transdermal pharmaceutical composition together with at least one additional anti-epileptic agent selected from clobazam, levetiracetam, topiramate, stiripentol, phenobarbital, lacsamide, valproic acid, zonisamide, perampanel, and fosphenytoin. The formulations maintain active agent delivery at a constant rate over an extended period, including continuous or constant rate of delivery over at least 7 days. The active-agent scope is based on synthetically produced cannabidiol and includes definitions directed to cannabidiol and tetrahydrocannabinol forms, salts, and derivatives.
The background problem addressed is seizure control in treatment-resistant epilepsy, including treatment resistant pediatric epilepsy and multiple listed seizure disorders and syndromes. The disclosed composition is presented in the context of reducing seizure frequency and achieving seizure-free outcomes in some patients, and the claimed subject matter provides an alternative transdermal delivery approach using highly purified synthetic cannabidiol with low tetrahydrocannabinol content. In vitro transdermal delivery behavior is supported by diffusion and release testing using human cadaver skin, including Franz diffusion cells, to report CBD flux and in-vitro release data across multiple synthetic CBD transdermal formulations.
Claims Coverage
The independent claim covers a drug-in-adhesive transdermal patch composition and delivery configuration. It includes inventive features related to the synthetically produced cannabidiol active agent amount, combination with specific anti-epileptic agents, specific adhesive and penetration-enhancer/suspending-agent/solvent/antioxidant components, and an equivalence to an oral dose delivered at a constant rate over at least 7 days.
Drug-in-adhesive transdermal patch with synthetically produced cannabidiol active agent
A transdermal pharmaceutical composition in the form of a drug-in-adhesive transdermal patch comprising about 1% to about 15% w/w of an active agent consisting of synthetically produced cannabidiol.
Combination with specified anti-epileptic agent
The transdermal pharmaceutical composition further comprises at least one additional anti-epileptic agent selected from the group consisting of clobazam; levetiracetam; topiramate; stiripentol; phenobarbital; lacsamide; valproic acid; zonisamide; perampanel; and fosphenytoin.
Silicon pressure sensitive adhesive patch matrix
The transdermal pharmaceutical composition comprises about 35% to about 99% w/w of at least one adhesive which comprises a silicon pressure sensitive adhesive.
Oleic-acid penetration enhancer and silicon dioxide suspending agent
The transdermal pharmaceutical composition includes a penetration enhancer which comprises oleic acid, and a suspending agent which comprises silicon dioxide at a concentration of about 2% to about 15% w/w.
Propylene glycol solvent and BHT antioxidant
The transdermal pharmaceutical composition includes a solvent comprising propylene glycol, and an antioxidant which comprises butylated hydroxytoluene (BHT).
Equivalent oral dose delivered at constant rate over at least 7 days
The pharmaceutical composition provides an equivalent to an oral dose in a patient selected from specified oral-dose ranges, at a constant rate of delivery of active agent over at least 7 days.
Overall, the claim coverage is directed to a specific drug-in-adhesive transdermal patch formulation using synthetically produced cannabidiol, combined with specified anti-epileptic agents, embedded in a silicon pressure sensitive adhesive matrix with oleic acid penetration enhancement and silicon dioxide suspension, using propylene glycol and a BHT antioxidant, and configured to provide an oral-dose equivalent via constant-rate delivery over at least 7 days.
Stated Advantages
Provides seizure-frequency reductions in treatment-resistant epilepsy and includes seizure-free outcomes in some patients.
Delivers active agent at a constant rate over at least 7 days.
Provides an equivalent to an oral dose in a patient selected from specified oral-dose ranges.
Documented Applications
Treatment of seizure disorders including complex partial seizures, simple partial seizures, partial seizures with secondary generalization, generalized seizures, absence seizures, grand mal seizures, tonic seizures, clonic seizures, status epilepticus, atonic seizures, myoclonic seizures, neonatal and infantile spasms, drug-induced seizures, trauma-induced seizures, febrile seizures, juvenile myoclonic epilepsy, Lennox-Gastaut, Dravet syndrome, Tuberous Sclerosis Complex (TSC), treatment-resistant epilepsy, treatment resistant pediatric epilepsy, mesial temporal lobe epilepsy, nocturnal frontal lobe epilepsy, progressive epilepsy with mental retardation, progressive myoclonic epilepsy, and seizures associated with CNS mass lesions.
A dosing regimen application specifying administration cadence selected from once in about 8 to about 13 days, once in two weeks, or once in 15 days to about 30 days.
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