Utility of Microcrystalline Cellulose for Improving Drug Content Uniformity in Tablet Manufacturing Using Direct Powder Compression.
Direct powder compression is the simplest tablet manufacturing method. However, segregation occurs when the drug content is low. It is difficult to assure drug content uniformity in these cases. In this study, we evaluated microcrystalline cellulose (MCC) as a segregation inhibitor in pharmaceutical powders. We assessed the influence of MCC concentration and mixing time on the physical properties of tablets. The tablet formulation comprised acetaminophen, lactose hydrate, cornstarch, MCC (0%, 10%, or 20%), croscarmellose sodium, and magnesium stearate (Mg-St). All powders except Mg-St were premixed for 5, 15, or 25 min. Mg-St was then added and mixed for 5 min to prepare nine pharmaceutical powders. Flowability index and practical angle of internal friction were measured. Tablets were also prepared, and their weight variation, hardness, friability, disintegration time, and drug content variation were evaluated. MCC slightly decreased pharmaceutical powder flowability. Tablet hardness increased and disintegration time decreased with increasing MCC concentration. MCC mixed for ≥ 15 min also significantly lowered drug content variation. A contour plot was prepared to assess the effect of MCC concentration and mixing time on the physical properties of tablets. It was determined that tablets with 50-80 N hardness, ≤ 3.5 min disintegration time, and ≤ 3% drug content variation can be prepared when MCC concentration is 6.5-8.5% and the mixing time is 19-24 min. Therefore, MCC is effective as a segregation inhibitor, and the addition of MCC to tablet formulation improves drug content uniformity.
['Nakamura|Shohei|S|', 'Tanaka|Chisato|C|', 'Yuasa|Hiroshi|H|', 'Sakamoto|Takatoshi|T|']
D002266:Carboxymethylcellulose Sodium D002482:Cellulose D004339:Drug Compounding D005079:Excipients D006244:Hardness D004364:Pharmaceutical Preparations D011208:Powders D011312:Pressure D013229:Stearic Acids D013607:Tablets
microcrystalline cellulose drug content uniformity segregation powder flowability design space