Leonard S. Rosenberg

Application of a Second-Order Derivtive Spectroscopic Technique: Determination of the Ionization Constants of Phenytoin and Phenobarbital

AbstractAbsorption spectroscopy can be used to determine the pK of a compound when a change in the spectral pattern can be related to a change in the protonation state of an ionizable group. The calculation of a pK becomes difficult (standard error increases) when these spectral changes are indistinct or are minimally resolved. In these cases, the ability of higher-order derivative spectroscopy to enhance the short-range fine structure of a spectra usually offers adequate spectral resolution for quantitative pK determinations.

An accurate prediction of the ph change due to degradation correction for a produced secondary buffering system

Esmolol hydrochloride degrades in aqueous solutions by the hydrolysis of a labile aliphatic carboxy-ester group. The products are methanol and ASL-8123. The resulting aliphatic carboxylic acid moiety (ASL-8123) has a pK of 4.80, which is within 1 pH unit of the pH of the formulation. ASL-8123 therefore acts as a “secondary buffer” and minimizes the change in pH due to degradation. Equations are presented to calculate the change in the pH when the primary degradation product acts as a secondary buffer. This information can be used in the development of a parenteral product to predict, a priori, the concentration of buffer necessary for optimal pH maintenance. This knowledge can reduce the number of formulation screens required to determine the necessary buffer capacity for optimal drug stability.