Associate Principal Scientist Merck & Co. West Point, Pennsylvania
The typical Excipients used in tablet formulation can induce the recrystallization of Spray Dried Intermediates (SDIs) during storage. Therefore, a novel approach was developed herein to illustrate the underlying mechanism of excipient-induced recrystallization of SDIs. The model SDIs were formulated with each commonly used excipient to make binary blend, binary compact, and bilayer tablet with controlled contact surface area. A significant difference in physical stability of tablets was observed with the different excipients: Mannitol and lactose can rapidly induce crystallization of model SDIs. However, SDI tablets formulated with MCC or starch showed a much slower rate of crystallization even with high moisture level. We found that Mannitol and Lactose not only can plasticize the SDIs but also function as seed to initiate SDI recrystallization in tablet. This presentation will show that excipient type, moisture level, and contact surface area were identified as three pillars to initiate recrystallization of SDIs.
Learning Objectives:
To learn the evolving recrystallization risk of spray dried intermediates in solid dosage forms (i.e. tablets/compacts)
To find out appropriate experimental strategies to tease-out the key excipients in tablets resulting in the recrystallization of spray dried intermediates
To reveal the underlying mechanism of excipient induced recrystallization in multi-component pharmaceutical tablets
To understand the risk of using mannitol and lactose as diluents in tablet formulation containing spray dried intermediates
To learn the key factors leading to the recrystallization of spray dried intermediates in formulation development of pharmaceutical tablet
