Measuring the distribution of density and tabletting force in pharmaceutical tablets by chemical imaging.
In pharmaceutical processing, the lubricant magnesium stearate (MgS) can affect compaction efficiency based on blend time and amount of MgS used. Insufficient lubrication produces intra-tablet variations in density. Consistent tablet density profiles and uniform compaction force, as managed by proper lubrication, are important for predictable performance. The current work demonstrates the utility of near-infrared (NIR) chemical imaging in measuring density variations within compacts, and relates these variations to tabletting forces as controlled by frictional properties and quantity of MgS. Lactose monohydrate was blended with 0%, 0.25%, or 1.0% MgS for 30s or 30 min. Compacts were prepared of each blend, with compaction forces monitored by load cells. Frictional properties were measured by automated shear cell. NIR chemical images were collected for each tablet, and the density at each image pixel was calculated. Density distribution within compacts was well perceived within the NIR images. Uniformity of intra-tablet density was strongly dependent upon friction between powder and die walls: tablets with no MgS or 0.25% MgS were less uniform than tablets with 1.0% MgS. In addition, absorbance variations along tablet edges, reflective of corresponding density variation, agreed with force transmission within the tablet and final tablet ejection force. Chemical imaging techniques can be used to non-destructively assess density profiles of tablets, and confirm prediction of friction alleviation and improvement in force distribution during tabletting. The density profiles were both qualitative, showing differences in density profiles between tablets of different blends, and quantitative, providing actual density and tabletting force information within a single tablet. This work demonstrates that near-infrared chemical imaging can be an effective tool in monitoring not only the physical quality of pharmaceutical tablets, but the corresponding die forces controlling tabletting and final ejection.
Ellison
Christopher D
CD
Division of Product Quality Research, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, United States. christophe.ellison@fda.hhs.gov
Ennis
Bryan J
BJ
Hamad
Mazen L
ML
Lyon
Robbe C
RC
D002626:Chemistry, Pharmaceutical / Q000379:methods; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods*; D019563:Mechanics; D011208:Powders; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D013229:Stearic Acids / Q000737:chemistry; D013607:Tablets / Q000737:chemistry*; D013672:Technology / Q000379:methods; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods*
D011208:Powders; D013229:Stearic Acids; D013607:Tablets; C031183:stearic acid