Guang-Jin Choi

Dynamic calibration for the in-line NIR monitoring of film thickness of pharmaceutical tablets processed in a fluid-bed coater.

NIR spectroscopy has been extensively employed for the in-line monitoring of pharmaceutical processes as one of the key PAT implementation tools. Nevertheless, pharmaceutical processes such as fluid-bed coating have not fully made the most of the NIR in-line monitoring primarily due to a difficulty in handling random in-line spectra. In this study, novel approaches to develop a reasonable dynamic calibration model were proposed; averaging and clustering. Pharmaceutical test tablets were coated with HPMC-based materials using a fluid-bed processor. During the 160 min coating process under tangential spraying mode, 10 tablets were sampled out at every 10 min mark for actual coating thickness measurements. NIR spectra at and near each 10 min mark were treated and processed by the averaging and clustering operations. Averaging of 21 spectra resulted in a reasonably good dynamic calibration model whose determination coefficient was estimated as high as 0.9916. The PCA-based clustering turned out to be substantially helpful especially when a large number of NIR spectra were averaged. A prediction experiment verified that our dynamic calibration model can control the coating thickness in-line as good as 3% deviated from the actual thickness, which can offer a reasonable end-point for the fluid-bed coating process.

Effect of molar ratio of KOH to Ti-isopropoxide on the formation of BaTiO3 powders by hydrothermal method

Abstract Nano-crystalline BaTiO 3 powders were prepared using acylated titanium and barium acetate with hydrothermal method. The solution pH given by the molar ratio of KOH to Ti-isopropoxide was found to have an important effect on the size, morphology, and crystallinity of BaTiO 3 powders. FT-IR and Raman analyses showed that there were still some Ba–OAc bonds in the structure of as-prepared powders formed from the low pH alkaline solution. As hydrothermal aging time increased, the crystal structure of as-prepared powders was continuously transformed from amorphous to crystalline BaTiO 3 powders with breakage of Ba–OAc bonds and elimination of acetyl groups in the powders. When the solution pH was high, most of the acetyl groups bonded to Ba or Ti atoms were eliminated rapidly by hydrolysis in the solution. As a consequence, crystalline BaTiO 3 directly precipitated from homogeneous solution via condensation reaction between –Ba–OH and –Ti–OH bonds without subsequent hydrothermal reaction.

Development of Process Analytical Technology (PAT) for Total Quality Innovation on Pharmaceutical Processes

The quality assurance issue of drug products is more important than the general product because it is highly related to the human health and life. In this reason, the regulatory guide lines have continuously been intensified all around the world. In order to achieve effective quality assurance and real-time product release (RTPR) of drug products, process analytical technology (PAT), which can analyze and control a manufacturing process, has been proposed from the United States. With the PAT process, we can obtain significant process features of materials, quality characteristics and product capabilities from a raw material to the final product in the real-time procedure. PAT can also be utilized to process validation using information system that can analyze the risk of drug products through out an entire product life-cycle. In this paper, we first offered a new concept for the off-line process design methods to prepare the improved quality assurance restrictions and a real-time control method by establishing an information system. We also introduced an automatic inspection system by obtaining surrogate variables based on drug product formulations. Finally, we proposed an advanced PAT concept using validation and feedback principles through out the entire life-cycle of drug product manufacturing processes.