Delphian Technology: in situ Monitoring with the RAINBOW Dynamic Dissolution Monitor® System

is a GMP and 21CFR Part 11 compliant instrument for pharmaceutical analysis.

The Rainbow Monitor is a powerful tool to aid those requiring multiple, accurate dissolution analyses performed with minimal operator involvement. The Rainbow Monitor can be used in conjunction with all major dissolution baths used in pharmaceutical laboratories, such as VanKel, Distek, Hanson, Sotax, etc. Part of the power of the Rainbow System stems from its ability to act as a dissolution monitor, spectrophotometer, and data analyzer, simultaneously. No longer is it necessary to run a dissolution on one system, transfer the sample to another system for analysis (UV spectrophotometer or HPLC), and then process the data and analyze results on a third system containing spreadsheets and graphical representations.

The Rainbow Dynamic Dissolution Monitor® system, powered by the versatile Rainbow Dissolution SmartWare® software program, allows users to perform all of those functions in one integrated system.

The Rainbow Monitor utilizes a dip type UV probe to measure the amount of active drug released from a solid dosage form.

The Rainbow Monitor utilizes a dip type UV probe to measure the amount of active drug released from a dosage form. Typically, six UV transflectance probes are placed into separate vessels and reside in situ for the duration of the test. Each probe is connected to its own miniature photo diode array (PDA) spectrometer via a fiber optic light guide.

UV transflectance probes are placed in vessels and reside in situ for the duration of the test

Typically, six UV transflectance probes are placed into separate vessels and reside in situ for the duration of the test.

The Rainbow Monitor utilizes a series of Zeiss PDA spectrometers interfaced to a dip probe to generate real time dissolution curves. Each of the probes is placed into a dissolution vessel at the start of the dissolution experiment and remains in situ during the entire dissolution run. Energy from a source lamp is split by means of a fiber optic furcation cable with individual fibers coupled to one of a series of dip probes. The energy thus directed, transits a calibrated gap in the probe body. The gap, which is in the dissolution bath, has a reflecting surface on the opposite side that sends the energy, which has passed through the media into a return fiber. The energy transmitted by this return fiber is then analyzed by one of the Zeiss PDA spectrometers and converted to absorbance values.

The Rainbow Monitor utilizes a series of Zeiss PDA spectrometers interfaced to a dip probe to generate real time dissolution curves.

The sample taken is an "optical sample"; that is, no material is removed from the bath. This allows acquisition of a full UV spectrum (235 nm - 390 nm) from all vessels very rapidly. A typical system configuration might sample every 10 minutes for 24 hours in the case of a controlled-release formulation, or every 5 seconds for an immediate-release formulation. Faster sampling rates are possible if fewer vessels are sampled. If a single probe is used, the scan rate can approach one scan per second.

Chart: Fiber Optic Probe Data Compared with HPLC Data

A dissolution curve is generated in real time by the Rainbow Dissolution SmartWare® software using the measured absorbance data and relating it to a set of previously analyzed standards to determine the percent the active ingredient dissolved as a function of time. The data that is generated is automatically stored in a secured database.

The Rainbow Monitor is easy to operate, and it requires almost no maintenance, as there are no moving parts in the system. The only maintenance that is required is light source replacement approximately every 2000 hours of use.

Rainbow does not generate any waste. The Rainbow monitor occupies little bench space in the laboratory and should be placed next to the dissolution bath. The system requires a PC to be able to perform all calculations and store generated data. The PC can be located remotely from the Rainbow Monitor — not necessarily on a lab bench.

The Rainbow Monitor is a powerful tool to aid those requiring multiple, accurate dissolution analyses performed with minimal operator involvement.

Optical Specification
The Zeiss MMS spectrometer exhibits excellent analytical performance in the absorbance range of 0.02 Au up to 1.00 Au. Because of its low thermal expansion properties, the titanium body of the Zeiss spectrometer minimizes drift due to heating and cooling. The patented design of the Zeiss MMS eliminates moving parts to ensure wavelength accuracy. (We have observed less than 0.1 nm annual drift.)

Optical entrance
The fiber optic cable consists of approximately 15 quartz glass fibers with 70µm core diameter each, designed as cross section converter. Fiber bundle input round: diameter 0.4 mm NA = 0.2 mounted in SMA-coupling mechanical tubes centric to the optic axis diameter outside: 25 mm diameter inside: 16 mm NA = 0.2 70, µ X 1250 Am

Grating
Flat-field, 1084 I/mm (center) blazed for approximately 220 nm

Spectral Range
200 nm - 390 nm (190 nm - 380 nm slit version) specifications for the range 235 nm - 390 nm

Wavelength accuracy absolute: Temperature-induced drift:
Spectral distance of pixel:
0.2 nm (CSC version)
< 0.005 nm / °C (CSC version)
Pixel ~ 0.8 nm

Resolution
(Rayleigh-criterion): ~\Rayleigh ~ 3 nm
Sensitivity: ~ 1011 - 1012 Counts/VVS (with 14-Bit conversion)

Stray light: 0.04% Deuterium lamp
Signal by 230 nm with Na3-Filter (1 g/l) to maximize signal without filter. Blocking filter for the second order is directly coated on the diode array.