OH Catalyzed Degradation of Barbiturates

Importantly, barbiturates posed certain serious hydrolytic problems with regard to their incorporation in the liquid dosage formulations, such as parenterals and elixirs. It has been duly observed 

Example. Phenobarbital [Gardinal ]. The following scheme vividly explains the base hydrolysis of phenobarbital wherein the cyclic ureide ring (in barbiturate) undergoes cessation. Besides, it may also be seen that the aforesaid cessation strategically takes place either between C-l/C-2 and/or C-l/C-6 locations in the structure of barbiturate. However, the cleavage between C-1 and C-6 is considered to be the most preferred pathway prevailing in the ionized barbiturates , such as aqueous solutions of sodium salts. 

Therefore, to pervent the said cleavage between C-1 and C-6 in phenobarbital it is absolutely necessary to stabilize its liquid dosage forms (e.g., elixir) at pH 6.0. At this specific pH the resulting hydroalcoholic solution remains fairly stable.  

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