Original by Mu Yiyang, Pharmaceutical Affairs Review, June 28, 2021

Powder refers to an aggregate composed of countless solid particles, and powder science, as the name suggests, is the discipline that studies the fundamental properties of powders. The terms “particles” and ‘powders’ frequently mentioned in our daily research work both fall under the category of powders. The primary distinction between them lies in particle size: particles with a diameter <100μm are termed “powders.” Due to their smaller size, interactions between particles are more likely to occur, resulting in poorer flowability. Particles with a diameter >100μm are termed “particles.” Contrary to powders, the self-weight of these particles exceeds the interparticle interactions, leading to better flowability. The powder properties of pharmaceuticals primarily include: particle shape and size, particle size distribution, density, flowability, wettability, or hygroscopicity. In routine formulation development, we often need to process APIs or excipients through grinding, mixing, and sieving. When the powder properties of raw materials are poor, we may select excipients with superior powder properties to improve the powder characteristics of the active ingredient. The primary objective of these processing steps is to enhance powder properties to meet subsequent formulation processing requirements. Consequently, the study of powder properties holds significant importance in solid dosage form development and application. If the powder properties of raw materials or granules are poor—for example, exhibiting poor flowability—it may affect tablet compression or the dosing accuracy of powdered formulations. Alternatively, the porosity or pore morphology of the drug may affect tablet disintegration, dissolution, and even absorption. Therefore, we will now explore the key powder properties studied in formulation research and their potential impacts on formulation processes. Fundamental Properties of Powder Particles 1. Powder Density and Porosity Powder density refers to the mass per unit volume of powder. Due to particle surface roughness and irregular shapes, voids exist when particles interlock. Additionally, some particles contain internal pores, giving distinct meanings to powder volume and density. In solid dosage form development, powder density is expressed as either bulk density or tap density. Bulk density, also known as apparent density, is measured by dividing the mass of powder filling a container by the container's volume without applying external force. Compaction density is determined by applying a specific force. The powder is vibrated to compact the freely piled material. This process continues as the number of oscillations changes. When the compacted volume no longer changes, the material is in its most densely packed state, yielding the compaction density. One method to indicate powder flowability is using the compression ratio: Compaction ratio generally indicates material flowability: a larger difference between measured loose density and tapped density suggests poorer flowability, meaning a higher compaction ratio. Flowability is considered good when the compaction ratio is below 20%; an increasing compaction ratio indicates reduced flowability, potentially leading to significant fluctuations in tablet weight or capsule filling weight during compression or filling processes. Porosity refers to the ratio of voids within a powder layer. Porosity is also a parameter significantly influencing powder processing properties and formulation quality, as it affects drug disintegration and dissolution behavior. Generally, higher porosity leads to faster disintegration and dissolution, facilitating greater drug absorption in the body. It can typically be calculated from true density or determined using methods such as gas adsorption or compression pumping.

2. Angle of Repose Measurement The angle of repose refers to the angle formed between the free surface of a powder pile shaped into the steepest possible cone and the horizontal plane. It serves as another indicator of powder flowability. Common measurement methods include the injection method, discharge method, and inclination angle method. Data obtained from different methods may vary, and reproducibility is generally poor. Particularly for powders with smaller particle sizes or higher viscosity, their poor flowability typically results in larger measured angles of repose. Generally, an angle of repose ≤30° indicates good flowability; ≤40° meets production flow requirements; >40° signifies poor flowability, potentially affecting dosage consistency in powders or capsules, or causing significant weight variation in tablet compression. Mitigation measures are necessary for such issues.

3. Particle size, sieve size, effective diameter, specific surface area, and equivalent diameter are measured through various methods. Among these, sieving is the most widely used, simplest, and fastest technique for determining particle size and size distribution. The sieving method involves: Arrange sieves of different mesh sizes from coarse to fine in sequential order from top to bottom. Weigh a specified quantity of powder according to the Chinese Pharmacopoeia method and place it on the topmost sieve. Vibrate the sample in a sieve shaker for a defined duration.