Improving Robustness of Pharmaceutical Dosage form Sample Preparation Using Experimental Design and Process Understanding Tools

Abstract

As a result of the excipient materials added to the drug substance to create a formulated pharmaceutical product, the preparation of drug product samples for chromatographic or other quantitative analysis can be manually intensive and time-consuming. It is therefore important that enough focus is placed on this aspect of method development to ensure accurate and reproducible results are obtainable across different laboratories. This paper outlines some of the challenges encountered when developing quantitative assay methods which are attributable to sample preparation procedures for solid-oral dosage forms (i.e. tablets and capsules). Approaches utilising experimental design, data visualisation and process understanding tools are described to highlight the importance of common sample preparation factors on drug recovery in product formulations. For a tablet formulation, experimental design highlighted that the percentage of organic in the sample diluent and the orbital shaker speed were statistically significant and could impact accuracy of assay result. For the second formulation, a gelatin capsule, the use of experimental design and the Britest process understanding tools highlighted the initial volumetric flask fill volume required close control to ensure reproducible assay results while the stand time (time sample left to stand post-shaking to aid analyte solubilisation) and capsule storage conditions were also significant.