Continuous manufacturing of solid oral dosage forms is promising for increasing the efficiency and quality of pharmaceutical production and products. In this study a whole train continuous direct compression (CDC) line has been provoked using challenging formulations typically prone to segregation in batch powder processing. Industrial compositions including components with variable size, bulk density and cohesive nature were selected. An experimental design, including variables such as API/mannitol particle size, API amount, powder feed rate and mixer speed, enabled the output quality of the provoked process to be assessed. Contrary to previous studies, a broader range of finished tablet quality attributes were probed, including content, uniformity of content, tensile strength as well as release performance. Overall, the continuous direct compression line was found to be a capable and efficient manufacturing process for the challenging compositions studied and surprisingly tolerable to handle the materials susceptible to segregation in typical batch settings. As expected, and given the 'fixed' apparatus configuration used in this study, the particulate material properties were found to have the most significant impact on the finished tablet quality attributes. The results emphasize the importance for taking a holistic approach when developing the operational windows and the strategy for control, e.g. by integrating the appropriate material properties, the actual apparatus design, and the relevant formulation design. The CDC line's ability to handle cohesive materials also seem to be one of the key advantages, thus confirming the recent promising results from other continuous direct compression studies.
Abstract. Magnesium stearate (MS) is the most commonly used lubricant in pharmaceutical industry. During blending, MS particles form a thin layer on the surfaces of the excipient and drug particles prohibiting the bonding from forming between the particles. This hydrophobic layer decreases the tensile strength of tablets and prevents water from penetrating into the tablet restraining the disintegration and dissolution of the tablets. Although overlubrication of the powder mass during MS blending is a wellknown problem, the lubricant distribution in tablets has traditionally been challenging to measure. There is currently no adequate analytical method to investigate this phenomenon. In this study, the distribution of MS in microcrystalline cellulose (MCC) tablets was investigated using three different blending scales. The crushing strength of the tablets was used as a secondary response, as its decrease is known to result from the overlubrication. In addition, coating of the MCC particles by MS in intact tablets was detected using Raman microscopic mapping. MS blending was more efficient in larger scales. Raman imaging was successfully applied to characterize MS distribution in MCC tablets despite low concentration of MS. The Raman method can provide highly valuable visual information about the proceeding of the MS blending process. However, the measuring set-up has to be carefully planned to establish reliable and reproducible results.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.