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.     

Left ventricular apical rotation is related to ambulatory blood pressure and body mass in healthy elderly females

OBJECTIVE: The interaction between left ventricular (LV) apical rotation, blood pressure (BP) and body mass in elderly females may reveal mechanisms involved in the syndrome of diastolic heart failure. METHODS: Thirty-one healthy females, age 69-84 years, were studied with echocardiography, ambulatory BP and an exercise capacity (VO2peak) test. RESULTS: LV apical short-axis loops were eligible for speckle tracking analysis in 27 subjects. Peak apical rotation (PAR) correlated inversely with diastolic BP (r = -0.47, p = 0.01). PAR correlated positively with stroke volume and body weight (p<0.05), but not with VO2peak (n = 19, p = ns). PAR also correlated with peak rotation velocity in systole (r = 0.76, p<0.0001) and in diastole (r = 0.58, p = 0.001). Diastolic peak rotation velocity correlated with mitral E wave peak velocity (r = 0.48, p = 0.01). There was a significant reduction in LV volumes during the 4 years of follow-up. CONCLUSIONS: In healthy elderly females, there seems to be an interaction between LV apical rotation, BP and body mass. Peak apical rotation and peak diastolic rotation velocity correlate with indices of LV filling and ejection, indicating that suction, a crucial element for effective early LV filling, may be preserved in healthy elderly subjects. Suction deteriorates with elevations of the arterial BP. An age- and BP-related reduction in LV end-diastolic volume may represent an additional impediment to LV filling. Both features may contribute to the development of LV diastolic dysfunction and to episodes of diastolic heart failure.