Multi-scale pharmaceutical process understanding: From particle to powder to dosage form

Understanding the properties and behavior of pharmaceutical materials is critical to the design of a safe and effective dosage form. The desired performance of pharmaceutical products differs from other areas of engineered material products. With pharmaceutical products, there is an increased level of importance on solubility, dissolution and stability; while a secondary level of importance is given to mechanical properties. The use of multi-scale process understanding suggests incorporating data from the different scales (particle, powder, and dosage form) into a single informatics database. The properties of the active pharmaceutical ingredient and the excipients must be interrogated at each scale. At the particle level, the primary concerns are with solubility, dissolution rate, the anisotropic properties of pharmaceutical crystals, polymorphism and the degree of crystallinity. At the level of the powder scale, the primary concerns are powder flow and the ability of the bulk powder to be compacted into a dosage form. Finally, at the dosage form level, critical issues include the effect of excipient crystallinity on dosage form dissolution rate and the tensile strength of compacts made from milled, roller compacted ribbons. Examples of existing and emerging approaches for understanding these properties and behaviors at each scale are illustrated as key elements in developing a multi-scale process understanding of a pharmaceutical process.