Uniformity of drug content during pharmaceutical dry granulating by roller compaction and tableting processes

Abstract

Purpose : To evaluate the usefulness of dry granulation by roller compaction in pharmaceutical tableting processes. Methods: Acetaminophen (AAP) as a model drug, lactose, corn starch, microcrystalline cellulose as excipients and magnesium stearate (MgSt) as a lubricant were used. Granules were prepared with a roller compactor and a mill, and then tablets were compacted with a rotary tableting machine. Uniformity of drug content in flakes, granules and tablets was examined with HPLC. Hardness, weight and disintegration time of tablets were also examined. Results: Tablet hardness increased with increasing compression pressure and with decreasing content of AAP. With low AAP content, tablet hardness increased with increasing roll pressure. With high content of AAP, tablet hardness decreased with increasing roll pressure. Disintegration times were also affected by compression pressure, AAP content and roll pressure. High roll pressure prolonged the disintegration time with low AAP content, but did not prolong the disintegration time with high AAP content. The coefficients of variance for AAP content averages of granules were clearly lower than those for flakes, and those for tablets were lower than those for granules. The coefficients of variance for 0.1% AAP tablets were relatively higher than those for other formulations, although the values were still low enough. Conclusion: The uniformity of drug content was highest in tablet form, showing that uniformity progressed with granulating, milling, mixing with lubricant and tableting. The tableting process with roller compaction can produce AAP tablets with sufficient content uniformity.