In Situ Spectrometers Deliver Fast Solution

Daniel C. McCarthy

Most pharmaceutical laboratories operate on limited time. Once patented, a new drug substance must navigate development and clinical trials before its manufacturer can see a return on its investment. The more sales made during the remaining life of the patent, the greater the profits.

Delphian Technology's dissolution monitor, used for pharmaceutical analysis, immerses ultraviolet transflectance probes directly into the test vessels to obtain measurements in situ. Thus, it avoids errors associated with sample transfer. Courtesy of Delphian Technology LP.

Improved speed and functionality were the goals for the development of the Rainbow dissolution monitor from Delphian Technology LP. Dissolution, a standard pharmaceutical analysis that predicts how quickly active ingredients will be released once ingested, measures regular samples from a calibrated water bath into which a drug solid form has been released.

Conventional methods require transporting samples of the solution to a cuvette or sample vial for analysis. Besides increasing time and footprint, these methods remove a portion of the contents from the dissolution vessel, exposing the test to analytical error.

Developed by Purdue Pharma LP of Stamford, Conn., engineered and manufactured by tec5 AG and commercialized by Delphian, the Rainbow monitor measures dissolution in situ, avoiding the errors associated with sample transfer. The instrument multiplexes a deuterium light source into six to eight channels and transports it via fiber to a like number of probes immersed in the solution.

The probes, which are made by Hellma GmbH & Co. in Mulheim, Germany, monitor the rate at which the dissolving drug alters the transmissive properties of the solution and transfers the data for analysis to six to eight spectrometers supplied by Carl Zeiss Jena GmbH in Germany. From there, multiplexer electronics from tec5 allow all channels to be read out within one second, providing greater data density.

"For a 24-hour dissolution, 145 sampling points are taken -- vs. the usual three to five points -- once every 10 minutes, which provides a much better statistical base for any data analysis," said Valeri Melekhov, director at Delphian. "Also, if an analytical error were to occur at a single datum point, the entire experiment is [still] successful due to the large number of sampling points."

The Zeiss MMS UV spectrometers integrate 256 pixels per diode array and have a nominal detection range from 200 to 390 nm. The step from pixel to pixel is 0.8 nm, providing a 3-nm so-called Rayleigh resolution. "This shows the better spectral resolution," said Gert Noll, tec5's director of marketing. "The use of a diode-array-based spectrometer itself gives you some advantages in speed and accuracy."