Stabilization of phenobarbital sodium for injection

A pharmaceutical composition of phenobarbital sodium having an ethanol content in the range from about 10000 ppm to about 66000 ppm, wherein the pharmaceutical composition is made by reconstituting the lyophilized pharmaceutical composition of phenobarbital sodium;

• wherein when the lyophilized pharmaceutical composition is stored at 20-25° C. for 12 hours or 2-8° C. for 36 hours, the amount of total impurities in the lyophilized pharmaceutical composition does not exceed 0.2%,
• wherein phenobarbital sodium is present in a concentration from 10-200 mg/ml;
• and
• wherein the pharmaceutical composition is free of benzyl alcohol and propylene glycol.

A lyophilized pharmaceutical composition of phenobarbital or salts thereof having an ethanol content in the range from 10000 ppm to 66000 ppm, wherein an amount of total impurities in the lyophilized pharmaceutical composition does not exceed 0.2% within 24 months of storage at 20° C.-25° C.,

• wherein, said lyophilized pharmaceutical composition upon reconstitution with water for injection or an aqueous saline or an aqueous dextrose solution provides a stable reconstituted composition up to 12 hours of storage at 20° C.-25° C. or 36 hours of storage at 2° C.-8° C.;
• wherein, an amount of total impurities in the reconstituted composition does not exceed 0.2% within 12 hours of storage at 20° C.-25° C. or 36 hours of storage at 2° C.-8° C.;
• wherein said lyophilized pharmaceutical composition and said reconstituted composition are free of benzyl alcohol and propylene glycol;
• optionally wherein said lyophilized pharmaceutical composition and said reconstituted composition comprise HCl;
• and
• wherein said reconstituted composition is suitable for the treatment of neonatal seizure.

A lyophilized pharmaceutical composition of phenobarbital or salts thereof having an ethanol content in the range from 10000 ppm to 66000 ppm, wherein when the lyophilized pharmaceutical composition is stored at 20-25° C. for 12 hours or 2-8° C. for 36 hours, the amount of total impurities in the lyophilized pharmaceutical composition does not exceed 0.5%;

• and wherein the pharmaceutical composition of phenobarbital sodium is prepared by a process comprising the steps of:
• (a) preparing an aqueous solution of phenobarbital or a salt thereof in a concentration of 10-200 mg/ml;
• and
• (b) lyophilizing said aqueous solution to obtain the lyophilized pharmaceutical composition of phenobarbital or salts thereof;
• wherein,
• i) the phenobarbital or salts thereof used in step (a) contains an ethanol content at least about 10000 ppm;
• or
• ii) the aqueous solution according to step (a) contains an ethanol content at least about 10000 ppm;
• or
• iii) the lyophilized pharmaceutical composition of phenobarbital or salts thereof contains an ethanol content at least about 10000 ppm.