Material Characterization Solutions for Optimization of Pharmaceutical Tableting - 12/05/2012
Micromeritics AccuPyc II 1340 and GeoPyc 1360 Pycnometers can work in tandem to help optimize process design, manufacturing, and drug product performance of pharmaceutical powders and solid dosage forms. This dual instrument approach combines true (absolute) and envelop (bulk) volume measurements to determine true density, total pore volume, and percent porosity.
Many physical performance and production characteristics of powders, granules, and final solid dosage forms are determined largely by their relative densities. Monitoring the relative densities of APIs, excipients, blends, and roller compacts can provide valuable insight in formulation strategy, process design, and scale-up of manufacturing processes to achieve optimization of solid dosage forms. Density knowledge and the QbD methodology it imparts for drug substance and excipient powders can provide qualification for direct compression tableting or the need for wet or dry granulation. For dry granulations, envelope (bulk) density can be monitored as an in-process method to track roller compact properties and to ensure the uniformity of total pore volume, stability, and physiochemical attributes of the finished final dosage form.
Pharmaceutical scientists realize that many of the physical, mechanical, and pharmacokinetic properties of tablets are influenced by the basic settings of a tablet press. The choice of tablet press operating conditions and tablet characteristics such as size, shape, and porosity influence the dissolution behavior of the tablets that are produced. Using the AccuPyc coupled with the GeoPyc, scientists are able to determine quickly and easily the true density, envelope density, total pore volume, percent porosity, and closed-cell pore volume of tablets produced with varying press settings. These measurements can also help ensure the manufacture of uniform tablet dosage forms when using multiple tablet presses.
Both pycnometers are based on Archimedes’ displacement principle. The AccuPyc II is a fully automated instrument that utilizes a gaseous displacement medium, typically nitrogen or helium. The pressures observed upon filling the sample chamber, then discharging the displaced gas into a second empty chamber allow computation of the sample solid phase volume. The GeoPyc uses a quasi-fluid displacement medium composed of microspheres having a high degree of flowability that do not wet the sample or fill its external or internal pores. A variety of sample chambers is available to accommodate a wide range of sample sizes and shapes.