Chapter 35 – Process Analytical Technology in Solid Dosage Development and Manufacturing

Publisher Summary Process analytical technology (PAT) is based on the use of inline/online or atline tools to determine product quality. Ideally, test results need to be available in a timely manner to allow for feedback control. Several techniques that have been introduced into pharmaceutical development include vibrational spectroscopy, acoustics, thermal effusivity, chromatography, laser diffraction, and optical techniques. Multivariate data analysis is necessary whenever the data obtained is in more than two dimensions. Traditional two-dimensional data are obtained for a thermocouple in a process. The data are in the form of temperature versus time. These data can be analyzed readily, as temperature is presented in terms of one variable: time. In the case of spectroscopic data, absorbance is obtained as a function of wavelength. When spectroscopic data is collected in real-time, an additional time dimension is added. The data is then presented in terms of two variables: wavelength and time. The main product quality attributes in encapsulation are content uniformity, and capsule weight. Monitoring encapsulation is challenging, due to the speed of the encapsulator and the need to monitor the powder inside the capsule before the cap is closed. Both near-infrared (NIR) and soft X-ray techniques have been used in real-time on commerical encapsulators to monitor content uniformity and fill weight, respectively.