A process analytical technology approach for the production of fixed-dose combination tablets of zidovudine and lamivudine using near infrared spectroscopy and chemical images

The production of solid drugs generally consists of several steps, which are monitored using quality control assays. In this work, rapid and non-destructive methods, which conform to the principles of the process analytical technology (PAT) framework, were developed for monitoring the production of fixed-dose combination tablets of zidovudine (AZT) and lamivudine (3TC). NIR spectroscopy was employed to determine the content of AZT and 3TC at three different steps of production: in the granulate material, in the core and in the manufactured tablet. NIR chemical images (NIR-CI) were used as a complementary study to evaluate the chemical distribution on the uncoated tablet surfaces, and its internal correlation structures. NIR methods for monitoring the moisture content in the granulate material and the hardness of the tablets before the coating step were also developed. A comparison between two multivariate calibration techniques: PLS and MLR was carried out. The models showed accurate results and prediction errors below those allowed by the regulatory agencies. Through the concentration maps associated with multivariate analysis, the internal chemical structure of API distribution and the excipient increased the understanding of the mixing process, allowing for further improvements.