Development of quantitative assays for the actives in intact pharmaceutical capsules using near-infrared spectroscopy

Near-infrared spectroscopy (NIRS) has been used for the analysis of drugs in intact tablets, but there are no publications in the scientific literature examining intact capsules. Two NIR spectrometers in reflectance and transmittance modes were used to determine the optimum way of developing such assays for capsules.;The knowledge gained was used to develop an assay of paracetamol in intact Boots' paracetamol 500mg capsules. The concentration of paracetamol in the capsule contents was 96.2%m/m and a relative standard error of prediction (RSEP) of 0.6% was obtained. The assay was developed to the standards of the International Conference of Harmonisation Guidelines on validation of analytical procedures. This assay would be suitable for batch release purposes.;Other assays for drugs were also developed to determine how generally applicable NIRS assays were to capsule products. The RSEP was found to rise as the concentration of the active decreased. The assay for paracetamol in Sainsbury's paracetamol 500mg capsules gave an RSEP of 1.76% for an active concentration of 83.3% m/m and a Sanofi-Synthelabo development compound (100mg) gave RSEP values of 6.1% and 9.4% respectively for intact capsules.;Finally, detailed practical guidelines were produced to develop NIRS methods for the assay of actives in intact capsules and how to prove the specificity of a non separative technique like NIRS, for use by the pharmaceutical community.;Transmittance was found to be the better of the two modes; three special sample plates were made to allow measurements in different orientations of the capsules. Measurements at one end of the capsule, whilst it was in a horizontal position, gave the best results. Spectral properties of capsules were investigated in detail to understand how best to optimise further the measurements in a pilot study. Calibrations based on concentration were better than those based on weight.