Solid oral dosage forms represent the predominant method of delivering ac,ve pharmaceutical ingredients (APIs), constituting up to 80% of all administered medications (Eggenreich et al., 2016). Among these, immediate release tablets stand out as the preferred choice for various reasons, including their ease of administration, precise dosing, high patient adherence, and extended shelf life (Bredenberg et al., 2003). In many cases, the industry utilises a granulation process – with wet granulation as a common choice – to improve manufacturability of the drug substance. Wet granulation involves enlarging particle size through liquid binding agents, offering control over granule and final product aZributes.
There has been significant progress in developing process models for granulation, but there is a demand for more accurate models depicting granule functionality. Mechanistic models are sought a\er to predict key rate processes of granules that describe its disintegration for predicting product performance. The limited understanding of granule performance is also linked to a lack of suitable measurement techniques that probe the fundamental disintegration mechanisms.
In-vivo disintegration initiates when a patient ingests an oral dosage form and it encounters physiological fluids, starting with saliva as the initial fluid. While saliva may not be the primary fluid facilitating most disintegration processes for many dosage forms, it serves as a crucial initial phase. Subsequently, the oral dosage form navigates through the gastrointestinal tract, where the bulk of tablet disintegration and dissolution takes place (Markl and Zeitler, 2017).
In both in-vivo and in-vitro disintegration, the tablet undergoes the same physicochemical changes as part of the disintegration and dissolution processes. There are a number of bonds within a tablet that must be broken for disintegration to take place; this includes cohesive forces (hydrogen bonding, van der Waals and electrostatic interactions) and mechanical interactions (solid/binder/crystalline bridges and mechanical interlocking) (Ellison et al., 2008). Disintegration is the breakdown of tablets into smaller pieces; this generates a larger surface area which enables dissolution to take place more rapidly. Incomplete disintegration limits the surface area available for dissolution and therefore hinders drug release. To negate this potential issue pharmaceutical formulations will o\en have a disintegrant added.