The importance of pycnometry in characterizing tableted medicines and pharmaceutical ribbons

Porosity, particle and pore size, as well as surface area can play an important role in achieving successful results in the manufacture of pharmaceutical products as well as in the formulation of active principle or excipients. Envelope density can be used to check tablet consistency and, when corrected for the skeletal density, it is commonly used to determine the total porosity in pharmaceutical ribbon manufacturing. Porosity and pore volume, as well as size distribution, affect how easily a solvent penetrates the solid matrix of tablets, thus forecasting the speed of solubility. The same parameters are important in the development of support for controlled drug release. Pore size is then often used to characterise artificial ceramic bone grafts that attempt to reproduce the natural porosity of human bone. New drug carriers based on specific MOFs have very narrow pores (below a few nm in size) and very high surface areas. For these materials, the investigation of the specific surface area and the distribution of the nanopore size (< 100 nm) are achieved by gas adsorption techniques (i.e. BET and NLDFT). Total pore volume and porosity can be calculated easily and quickly by measuring the bulk or envelope density of a material in combination with the skeletal density. Envelope density can be measured by two techniques, namely mercury porosimetry (Autopore V) or quasi-fluid powder displacement technique (measured by the GeoPyc, a unique instrument available on the market and developed by Micromeritics Corporation). Skeletal density is measured by gas displacement, usually helium, although other gases can be used in the standard AccuPyc instrument. Pore volume, particle and pore size, bulk and apparent densities are measured by mercury intrusion porosimetry over the widest pore size range available, from more than 600µ down to 3.6 nm. Finally, for narrower pores below 100 nm and for a proper evaluation of the specific surface area, the gas adsorption technique can be applied using specific instruments from Micromeritics (3Flex, Tristar or Gemini).