(M1130-10-57) Evaluation of Lubricant Distribution in Tablets Using All-in-One Excipients

Purpose: In the production of pharmaceutical tablets, lubricants are used to prevent tableting issues and to give the lubricity to tablet surfaces. Furthermore, the addition of  lubricants are expected to improve the flowability, fillability, to prevent adhesion of the powder. Therefore, lubricants are essential for general tablet formulations and they are important excipients for improving tablet quality and manufacturing efficiency.[1] Lubricants are generally mixed with other ingredients just before tableting process. However, the excessive addition and/or mixing before tableting would result in decreasing tablet hardness and/or delaying dissolution time. To solve these issues, an external lubrication method was developed in which lubricant is sprayed onto the surface of punches and dies in a tableting machine. Nevertheless, this method does not provide a fundamental solution because it is difficult to accurately control the amount of lubricant added to the tablets (less than a 1 mg).[2] Therefore, we developed a novel All-in-One Excipient which require no addition and mixing lubricants just before tableting.

Methods: The All-in-One Excipient (AOE) is composite granule which was prepared with mannitol (Man), microcrystalline cellulose (MCC), a super disintegrant, and sodium stearyl fumarate (SSF). This is formulated with 1% for SSF. The Co-Processed Excipient (CPE) for comparison was prepared with the three ingredients of the AOE formulation, excluding SSF. These were prepared by spray drying process. AOE did not add any other ingredients just before tableting. On the other hand, CPE mixed with 1% for SSF as a lubricant. Tablets were prepared by each powder using a rotary tablet machine and evaluated. (Fig. 1)

Results: In the case of the CPE, powder adhered to the punch after tableting. However, in the case of the AOE, no powder adhesion to the punch was observed. After further study, we found that an addition of 3% for SSF was required to obtain sufficient lubricity. Therefore, it was revealed that the use of AOE formulated with the lubricant could improve lubricity and reduce the amount of lubricant required. The distribution of the lubricant in the tablet was confirmed by an electron probe microanalyzer (EPMA). The results showed that the AOE tablets had a more uniform distribution of SSF compared to the CPE tablets. Therefore, we considered that the difference in the distribution state of SSF affected the lubricity of the tablets. (Fig.2) Furthermore, when ethenzamide or acetaminophen was added at 30% as an active pharmaceutical ingredient to AOE, tablets of practical hardness could be prepared without any tableting issues.

Conclusion: In order to simplify the tablet manufacturing process and to solve the issues of lubricants, we developed the novel All-in-One Excipient formulated with the lubricant. As a result, we found that the All-in-One Excipient efficiently imparts lubricity by distributing the lubricant uniformity in the tablet compared to the co-processed excipient in which the lubricant was added later.

References: [1]　J. Soc. Powder Technol., Japan, 47, 388-393 (2010)
[2]　J. Pharm. Sci. Technol., Japan, 71 (4), 223-227 (2011)

Fig. 1：Scheme of tablets preparation

Fig. 2：Distribution of SSF in the part of tablet（Left：AOE tablet　Right：CPE tablet）