Development of assays for the active in intact pharmaceutical capsules using near-infrared spectroscopy.
AAPS Pharmaceutical Sciences
Purpose: To study the problems associated with capsule measurements using NIRS. Develop an assay for the active in intact Paracetamol capsules in line with the ICH guidelines and develop guidelines on the measurement of the active in capsules for those interested in capsule analysis. Methods: NIR instruments - Buhler?s NIRTAB and FOSS NIRSystems were used for the studies. Boots? paracetamol capsules were presented horizontally, slanted and vertically. Reference method ? UV spectroscopy. Calibration samples were based on addition of the two major excipients (magnesium stearate and sodium glycollate) and pure paracetamol to the original powder-79% to 96.94% m/m active). 52 Boots? calibration mixtures in capsules were measured over the range 6000 ? 11520 cm-1. NIRCAL 3 software was used to control and process the data. Samples were randomly divided into calibration (35) and validation (17) sets along with their UV assay values. Spectra were mathematically treated by performing several data treatments, chemometric analysis. Calibrations were optimised for as small a SEP and SEE. Other parameters considered were consistency, validation bias, regression coefficient, etc. Results: Capsules measured at the end horizontally produced the best model with a SEP of 0.67%, SEE 0.61% m/m, calibration and validation regression set 0.99, , consistency 90.88 m/m using MSC and PLS. A paired t test suggested no evidence of difference between NIR and UV methods, bias and accuracy were 0.04% and 0.17%. Short term precision excellent (SD 0.17 to 0.55% m/m), intermediate precision (SD 0.33 and coefficient of variation 0.07% m/m). Conclusion: The one step NIR assay of paracetamol in Intact Boots' 500 mg paracetamol capsules was rapid and statistical analysis indicated it is comparable to British Pharmacopoeia 2001. This is the first reported assay for the active in capsules. The capsules were left intact and available for packaging or re-measuring and suitable for batch release purposes.
|Title:||Development of assays for the active in intact pharmaceutical capsules using near-infrared spectroscopy|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy|
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