In-line monitoring of powder blend homogeneity in continuous drug manufacture using near infrared spectroscopy
The pharmaceutical industry faces technical challenges in the near future when transitioning from the traditional batch wise manufacturing to continuous manufacturing.
One issue that needs to be solved is how to obtain high-quality measurements of a moving solid powder sample. The aim of this work was to study this issue. The first part was to develop an in-line near-infrared spectroscopy (NIR) probe holder to improve the sample presentation directly after the first of the two consecutive blenders in continuous direct compression (CDC).
The probe-holder collects the sample and momentarily holds it still during analysis. The second part of the work was to evaluate the in-house developed and commercial probe holder operating by the same principle. In-line measurements were conducted by simulating the discharge from the blend using a feeder. Both off-line and in-line orthogonal partial least-square (OPLS) prediction models were constructed using multivariate statistics. The models were pretreated using first derivative and standard normal variate (SNV) filters.
The possibility of in-line monitoring the active pharmaceutical ingredient (API) using an off-line calibration through local centring was also investigated. The off-line prediction model overpredicted the concentration with approximately 2 %. Local centring was used as a solution to the overprediction. However, the NIR spectra obtained from the samples used for local centring indicated that segregation had occurred.
Due to limited time, the powder blends could not be re-mixed and used to further investigate the possibility to use an off-line calibration to predict in- line measurements. The in-line calibrations could successfully predict the API con- centration in powder blends measured in-line. The in-house made and commercial probe holders showed similar results and were both fit for purpose.
Further investigation regarding for example cost and validation requirements should be made before deciding whether to continue with the solution of the in-house made probe holder or the commercial one. Download the full thesis: in-line-monitoring-of-powder-blend-homogeneity-in-continuous-drug-manufacture-using-near-infrared-spectroscopy.pdf