Two lubricants, magnesium stearate and sodium stearyl fumarate, were compared under identical mixing conditions to study their roles in drug-excipient interactions. After prolonged mixing, sodium stearyl fumarate did not interact with the drug or excipients; as a result, the disintegration time and drug dissolution rate from hand-filled, uncompacted capsules were not adversely affected. In contrast, magnesium stearate did exhibit drug-excipient interactions which resulted in lamination and subsequent adhesion of the lubricant to the drug-crospovidone agglomerates. These interactions adversely affected the disintegration time and drug dissolution rate from hand-filled, uncompacted capsules. Although the initial specific surface area of magnesium stearate was higher than that of sodium stearyl fumarate, flaking of magnesium stearate due to particulate-particulate interactions caused a large increase in the surface area. The adhesion of the magnesium stearate flakes to the drug-crospovidone agglomerates resulted in a decrease in the drug dissolution rate.