Micromeritics is recommending a twin approach to characterising materials for pharmaceutical powders and solid dosage forms, to optimise process design, manufacture and drug performance.
Using its AccuPyc II 1340 (gas displacement density analyzer) and GeoPyc 1360 Pycnometers (envelope density analyzer) in tandem, rapid and simultaneous measurements can be made of both true (absolute) and envelope (bulk) volume –from which true density, total pore volume and percent porosity can be calculated.
Relative densities are often the key to determining physical performance and production characteristics in powders, granules and final solid dosage forms. Insight gained from better information on relative densities of APIs, excipients, blends and roller compacts allows formulation strategy, process design and upscaling of manufacturing processes to be enhanced – resulting in optimisation of solid dosage forms.
Thorough understanding of densities is an important basis for QbD methodology in relation to drug substances and excipient powders. It can provide qualification for decisions between direct compression tableting and wet or dry granulation. Envelope – or bulk – density can be monitored, in process, when dealing with dry granulations. This method tracks roller compact properties and ensures that the final dosage form is uniform in total pore volume, stability and physiochemical attributes.
The settings and operating conditions of a tablet press, and the size, shape and porosity of the tablets produced, have a significant influence on the product’s dissolution behaviour and other physical, mechanical and pharmacokinetic properties.
By coupling AccuPyc and GeoPyc, a quick and simple determination can be made of the true density, envelope density, total pore volume, percent porosity and closed-cell pore volume of tablets produced using different press settings. The same measurements are also useful in ensuring uniformity of tablet dosage forms when multiple tablet presses are used in their manufacture.
Both instruments rely on Archimedes’ displacement principle for their measurements. The AccuPyc II is fully automated and uses a gaseous displacement medium. This is normally either nitrogen or helium. The sample’s solid phase volume is computed from pressures determined when the sample chamber is filled and then when the displaced gas is discharged to the second, empty chamber.
In the GeoPyc, the displacement medium is a quasi-fluid, composed of microspheres, with a high degree of flowability. This neither wets the sample nor fills its external or internal pores. A wide range of sample sizes and shapes can be accommodated using the variety of chambers available.