In situ dissolution testing using potentiometric sensors.
Potentiometric sensors can be used to determine the amount of API dissolved in the dissolution medium in function of time by measuring directly in the dissolution vessel of a Paddle (USP type 2) and Basket (USP type 1) apparatus. The prototype potentiometric sensor instrumentation showed very promising results for a selection of APIs with different physico-chemical properties. The applicability, benefits and limitations of the prototype were explored. The applicability of the measurement technique strongly depends on the log(P) of the API. Here, it is shown that measurements can easily be performed for APIs with a log(P)>4. Electrode performance however decreases with decreasing logP of the APIs due to decreased drug selectivity in comparison to the excipients and ionic strength of the applied dissolution medium. The potentiometric sensors are shown to be insensitive towards undissolved particles and air bubbles as opposed to UV spectrometric measurement where these can lead to severe light scattering. For the tested APIs, the obtained dissolution profiles are very reproducible and show a low variation compared to the measurements using manual sampling and UV or HPLC analysis. The measurements demonstrate that potentiometric sensors are a very promising technology that can become a standard for in situ dissolution measurements.
Johnson & Johnson Pharmaceutical Research and Development, a Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, Belgium. kpeeterb@prdbe.jnj.com
Karl
K
Peeters
Roy
R
De Maesschalck
Hugo
H
Bohets
Koen
K
Vanhoutte
Luc
L
Nagels
D002851:Chromatography, High Pressure Liquid; D002936:Cinnarizine / Q000737:chemistry; D004294:Domperidone / Q000737:chemistry; D004566:Electrodes; D004867:Equipment Design; D005079:Excipients / Q000737:chemistry; D005336:Fiber Optic Technology; D007654:Ketoconazole / Q000737:chemistry; D007700:Kinetics; D008139:Loperamide / Q000737:chemistry; D009391:Nephelometry and Turbidimetry; D009994:Osmolar Concentration; D011199:Potentiometry / Q000295:instrumentation*; D015203:Reproducibility of Results; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000295:instrumentation*
D005079:Excipients; D002936:Cinnarizine; D004294:Domperidone; D008139:Loperamide; D007654:Ketoconazole