Density and Porosity: The density of particles, powders, and compacts is an important property affecting the performance and

function of many pharmaceutical materials. MPS uses five different state-of-the-art tools to measure density. By definition, all density measurements involve the measurement of mass and volume. Mass is determined with an analytical balance and the key to obtaining reliable density values is in the accuracy and precision of measuring volume. Different types of density determined by MPS include: True Density: True density is the density of the solid material excluding the volume of any open and closed pores. Depending on the molecular arrangement of the material, the true density can equal the theoretical density of the material and therefore be indicative of how close the material is to a crystalline state or the proportions of a binary mixture. True density measurements can be preformed on APIs, excipients, blends, and monolithic samples such as tablets. MPS uses Micromeritics Instrument Corporations highprecision gas pycnometers, which are accurate to 0.02% of the sample volume to determine true density. Apparent Density: Apparent density is similar to the true density except the volume of closed pores is also included. Tablets or excipient materials may have closed cells or bubbles that are not accessible to the probe gas. In this instance, gas pycnometry produces the apparent density. If the true density of a powder is known and the density of a tablet composed of this same material differs, the closed pore volume can be determined. Closed pore volume may be linked to press performance and die filling, Bulk Density: Bulk density is a characteristic of a volume of divided material such as powders, grains, and granules. It includes the volume of the solid material, open and closed pores, and the interparticle voids. The total volume of interparticle voids can change with packing, thus leading to the concept of Tap Density, which measures the volume of a mass of sample after inducing a closer packing of particles by tapping the container. Taking this method to the extreme leads to the determination of void volume and compressed density after compressing the sample under extreme forces and measuring the volume change as a function of applied pressure. Envelope Density: Like bulk density, envelope density is determined from the volume of the solid material, open pores, and closed pores. Envelope density is determined for a single, consolidate quantity of material, therefore there are no interparticle voids between packed particles. Envelope density is the mass of the object divided by the volume within an imaginary, closely conforming skin that envelops it and, therefore, may include the volume of small surface irregularities. MPS routinely measures the envelope density of tablets, roller compacts or ribbons, lyophilized cakes, and granulations. When envelope and true density both are known, the total pore volume, percent porosity, and solid fraction of the sample can be calculated. Porosity: Porosity consists of volume of the pores relative to the envelope volume used to calculate envelope density. The porosity of pharmaceutical materials and medical devices can impact production, material movement, and pharmacokinetic behavior. Tablet porosity determines the tensile strength (hardness) of tablets for a given composition. Tablet porosity may be regarded as a measure of the tableting process. Variations in tablet porosity reflect various aspects of tablet press performance. Tablet porosity may relate to tablet disintegration and dissolution. In the case of coated tablets, coating quality may be affected by tablet porosity. Some excipients are porous by design

and variations in their porosity can impact product performance. New research suggests that some porous silicas can be used to process APIs and promote crystal changes. Other applications include granulations, roller compacts or ribbons, lyophilized materials (lyocakes), and coated medical devices. MPS has the capability to determine overall porosity as well as pore size distributions of many materials.