Enhanced Stabilization of Phenobarbital Sodium for Injection

This invention provides a novel system, method, and composition for stabilizing phenobarbital sodium for injection, ensuring improved efficacy, safety, and efficiency in neonatal seizure treatment.

The original patent disclosed a lyophilized pharmaceutical composition of phenobarbital or salts thereof with an ethanol content in a specific range. However, this composition may still degrade over time, leading to impurities and reduced efficacy. The present inventive concept addresses these limitations by introducing a system and method for minimizing total impurities during reconstitution, improving storage conditions, and formulating the composition to reduce impurity formation.

The novel system comprises a lyophilized pharmaceutical composition having an ethanol content in the range from about 5000 ppm to about 70000 ppm, and a reconstitution device for mixing the lyophilized composition with a vehicle/diluent. The method involves lyophilizing a pharmaceutical composition having an ethanol content in the range from about 12000 ppm to about 25000 ppm, and storing the lyophilized composition at a temperature range of 2-8° C. to reduce degradation. The composition is formulated to reduce the formation of 2-phenyl-2-ethyl acetyl urea impurities, ensuring a total impurity content of less than 0.1% following 36 months of storage at 20-25° C.

The inventive concept's novelty lies in the integration of a reconstitution device, controlled storage conditions, and a formulation designed to minimize impurities. This combination provides a significant improvement over the original patent, as it ensures the stability and efficacy of phenobarbital sodium for injection over an extended period.

Alternative embodiments may include varying the ethanol content range, using different vehicle/diluents, or incorporating additional stabilizers. Variations of the method may involve adjusting the storage temperature or using different lyophilization techniques.

This inventive concept has significant commercial potential in the pharmaceutical industry, particularly in the treatment of neonatal seizures. The improved stability and efficacy of phenobarbital sodium for injection can lead to better patient outcomes, reduced healthcare costs, and increased market share for pharmaceutical companies.