Drug Ionization and Physicochemical Profiling

Miniaturized Rotating Disk Intrinsic Dissolution Rate Measurement: Effects of Buffer Capacity in Comparisons to Traditional Wood’s Apparatus

“…Since many low-soluble NSAIDs can self-aggregate to form micelles and micelle-like structures above a critical concentration (43), determination of their pK a values from solubility-pH profiles can be unreliable (26,27,34,44,45). Possibly, the pK a value of ketoprofen at 37°C reported as 4.76 (21) and 4.60 (43) are "apparent" values (45), that differ quite substantially from the true pK a value of 4.02.…”

“…Possibly, the pK a value of ketoprofen at 37°C reported as 4.76 (21) and 4.60 (43) are "apparent" values (45), that differ quite substantially from the true pK a value of 4.02. Also, the McIlvaine buffer used for pH control (21), changes significantly in ionic strength over its working pH range (31), further challenging precise pK a determination by the solubility-pH method.…”

pKaDetermination

“…Physicochemical properties such as solubility in physiological media, octanol/water and phospholipid bilayer/water partition coeffi cients, bilayer membrane permeability, and reaction rates of ionizable drug molecules all can be infl uenced by the value of the p K a [4] . This ionization in turn affects their availability to enter into physical, chemical, and biological reactions.…”

“…There appears to be no specifi c theory that would allow a priori (e.g., from knowledge of 2D structure) temperature " correction " to p K a determined at non -standard temperatures, as, for example, compensations to the p K a values due to changes in the ionic strength are possible using the Debye -H ü ckel equation [Eq. 4 shows some examples of temperature coeffi cients of p K a values of common weak acids, bases, and ampholytes [1] . Table 3.…”

“…This is the Avdeef -Bucher (1978) [4] four -parameter electrode standardization, and most new practitioners in p K a determination will not be familiar with it. This is the Avdeef -Bucher (1978) [4] four -parameter electrode standardization, and most new practitioners in p K a determination will not be familiar with it.…”