Dissolution Kinetics of Carboxylic Acids II: Effect of Buffers

Mooney, K.G.; Mintun, Mark A.; Himmelstein, Kenneth J.; Stella, V.J.

doi:10.1002/jps.2600700104

Cited by 161 publications

(136 citation statements)

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“…In the tests performed at pH 7.4, somewhat higher fluctuations with values of ΔpH ranging from −0.03 up to −0.04 pH units were noticed immediately after purging. The observed "overregulation" is related to the slower reaction rate of CO 2 (gas) dissolution and dissociation as well as to test parameters, such as the amount of titer gas remaining in the tubing that connects the proportional valve with the diffuser, the electrode response and the mixing conditions in the USP Apparatus II (16)(17)(18)(19). However, both the dynamics and the precision of the pH adjustment can be regulated flexibly by appropriately setting the pressure of the titer gas introduced into the device as well as by the adjusting the device settings such as trigger pH difference, regulation range, and hysteresis.…”

Section: Discussionmentioning

confidence: 99%

An Automated System for Monitoring and Regulating the pH of Bicarbonate Buffers

et al. 2013

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Abstract. The bicarbonate buffer is considered as the most biorelevant buffer system for the simulation of intestinal conditions. However, its use in dissolution testing of solid oral dosage forms is very limited. The reason for this is the thermodynamic instability of the solution containing hydrogen carbonate ions and carbonic acid. The spontaneous loss of carbon dioxide (CO 2 ) from the solution results in an uncontrolled increase of the pH. In order to maintain the pH on the desired level, either a CO 2 loss must be completely avoided or the escaped CO 2 has to be replaced by quantitative substitution, i.e. feeding the solution with the respective amount of gas, which re-acidifies the buffer after dissociation. The present work aimed at the development of a device enabling an automatic pH monitoring and regulation of hydrogen carbonate buffers during dissolution tests.

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Section: Discussionmentioning

confidence: 99%

An Automated System for Monitoring and Regulating the pH of Bicarbonate Buffers

et al. 2013

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“…Although the effect of buffer rate-enhancement has been documented for various processes (reaction in immobilized enzyme systems (3), proton transport in muscle (4,5), drug dissolution (6)(7)(8)(9)(10)(11)), the use of buffers in polyelectrolyte gels remains largely unexplored. Much of the work on polyelectrolyte-gel swelling kinetics stresses the importance of solution conditions such as pH and ionic strength in influencing thecharacteristics of gel behavior (10)(11)(12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Buffer effects on aqueous swelling kinetics of polyelectrolyte gels

Chou

Blanch

Prausnitz

et al. 1992

J of Applied Polymer Sci

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Electrolytes are often added to a gel‐swelling medium under the assumption that the important conditions which characterize swelling rates are the solution pH and ionic strength, with little emphasis on the nature of the electrolyte. Previous research by Siegel et al. has indicated that the presence of the un‐ionized acidic form of an electrolyte buffer is a primary rate determinant for swelling of a polybase gel. A systematic swelling study on two separate gels, 2‐hydroxyethyl methacrylate copolymerized with methacrylic acid (HEMA/MAA) and N,N‐dimethylaminoethyl methacrylate (HEMA/DMA), has been performed to investigate the influence of the concentration of the un‐ionized buffer by three principal factors: (1) total buffer concentration, (2) solution pH, and (3) buffer pKa. Swelling and deswelling kinetics were obtained. In the presence of an electrolyte buffer, a dramatic swelling rate increase is observed for the HEMA gels, with substantial gains in rate obtained as total buffer concentration rises. Results also emphasize that to enhance swelling kinetics, the pH must be such that the buffer is essentially un‐ionized.

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“…The behaviour of indomethacin during pH-metric pK a measurement at 1 mM concentration when forming aggregates in the presence of 0.15 M KCl and varying percentages of solvent is likely to be hard to predict. The difficulty of accounting for aggregation might also explain why other reported measurements of indomethacin pK a differ considerably (4.01 +/-0.09, I=0.05 M, 25 °C, CE procedure [30]), (4.17, I=0.5 M, 25 °C [31], (4.5, conditions not described [29]). The effects of aggregation should be less apparent in UV-metric pK a measurement, where the sample concentration is around 30 μM.…”

Section: Methodsmentioning

confidence: 99%