Process Analytical Technology (PAT) is the important tools to understand the process, obtaining critical process parameters and used as process monitoring following by quality by design (QbD) concept. It has been applied to the pharmaceutical manufacturing especially in every step of tablet production until final product in order to ensure the product quality. Otherwise, it would be an essential part of a scientific-based pharmaceutical quality assessment due to the food and drug administration announcement.The purpose of this research is to show the application of PAT tools through tablet manufacturing process; blending by cube mixer, granulation by twin-screw extruder and including finished product properties. Critical process parameters were identified through design of experiments (DoE), and then data of each step was recorded by widely accepted PAT approaches (e.g. near-infrared spectroscopy, particle size analysers) before initiation of downstream process to strengthen scientific data of design space. Moreover, multivariate analysis software (SIMCA), was involved in order to extract multivariate spectroscopic data to be comparable form such as Principal component analysis (PCA). This formulation contained two active pharmaceutical ingredients (API), Paracetamol and Caffeine, while others studies contain one which was challenging of this study. Nevertheless, this formulation based on high shear wet granulation method, however it was successful to be granulated with twin screw extruder. However, more studies with screw configuration are still required to improve shapes on granules.Blending uniformity was firstly studied by ATR-IR spectroscopy and PCA showed similarity of data after 10 min of blending in all 3 batches.Therefore, DoE was employed to optimize three critical process parameters; solid feeding rate, liquid feeding rate and extruder speed. EYECON and QICPIC were utilized for obtaining particle size distribution during experiments; consequently, one configuration which provided the best unimodular-shaped PSD was selected and full batch granulation was performed. Near Infrared spectroscopy (NIR) was equipped in order to monitor the product content uniformity along batch granulating. Spectrum were analysed to be Hotelling T² plot against time and used as process signature for the future batches and scale enlargement. Finally, after tablet compression, ingredient mapping on the tablet surface was illustrated by Raman Microscope to ensure the uniformity of 2 active pharmaceutical ingredients on the tablet. Maps showed uniformly spreading of each API on the table surface.This studies were demonstrated that PAT tools can be involved along the process development, obtain data of attributes and be a part of decision tools. It could be a sample for involvement of PAT tools in the whole manufacturing process and could be further applied for an industrial production which corresponded to QbD concept to make better strategy for drug quality assurance for the next recent years.
|Date of Award||19 Sep 2016|
- University Of Strathclyde
|Supervisor||Dimitrios Lamprou (Supervisor) & Alastair Florence (Supervisor)|