Optical fiber spectrometry in turbid solutions by multivariate calibration applied to tablet dissolution testing

ples. The procedure is amed In tablet dissdutbn tests. The error of the callbration Is small compared with the varlaUon between individual tablets. Wlth the Increased amount of informatlon In spectra compared to slngle wavelength measurements, It ls also possible to monltor the quality of the measurement by residuals and scatter plots. Automation will be posslbie by a robot moving the probe. A novel analysis method for dissolution tests of tablets is described and applied to felodipine, an antihypertensive drug in an extended release formulation (I). The method involves spectrophotometric measurements by means of fiber optics made in turbid solutions without previous filtering of the sample. The turbidity interference is compensated for by multivariate analysis. In dissolution testing, the rate and extent of drug release of a pharmaceutical product are measured in an in vitro system (2). The results from the in vitro system are then correlated with in vivo measurements to obtain a test that can replace the in vivo process for quality control purposes. The dissolution test gives a good estimate of batch-to-batch consistency during production, is well established as a screening tool for formulation development, and is also used to verify that the tablet composition keeps the same properties until its expiration date. The common way to obtain samples from dissolution tests is by manual sample withdrawal or with a flow system that removes aliquots at preprogrammed times. The detection method is usually spectrophotometry, sometimes preceded by a chromatographic separation. Manual sample withdrawal is, however, not convenient for tablets made with a slow release rate of the drug because the dissolution test may take up to 24 h to complete. The flow approach has drawbacks too, since this drug is very hydrophobic and adsorbs to the plastic tubing commonly used in flow systems. It is also difficult to switch filters automatically in a flow system when the filter becomes clogged by the particles and colloids from the tablet matrix.