Drug-excipient interactions resulting from powder mixing. VI. Role of various surfactants

Abstract

The role of various surfactants on the drug-excipient interactions resulting from prolonged powder mixing with magnesium stearate was investigated. Drug-excipient formulations containing 0.5% magnesium stearate and 0.1–0.5% surfactants were compared with the same formulations without the surfactant under identical mixing conditions to study the effect of prolonged mixing on the in vitro dissolution of ketorolac tromethamine from hand-filled, uncompacted capsules. The results indicate that some surfactants in a concentration as little as 0.1% (1:5 w/w ratio to magnesium stearate) can alleviate the deleterious effect of magnesium stearate on the prolonged mixing of powder, i.e., the decrease in the dissolution rate of the drug. The effectiveness of the surfactants is determined by their hydrophilic-lipophilic balance (HLB) value and solubility, and increases with increasing concentration or decreasing particle size. The hydrophilic anionic surfactants (sodium N-lauroyl sarcosinate, sodium stearoyl-2-lactylate, and sodium stearate), non-ionic surfactant (poloxamer 188), and cationic surfactant (cetylpyridinium chloride) are as effective as sodium lauryl sulfate reported in a previous study. Conversely, the lipophilic surfactant, glyceryl monostearate, failed to offset the deleterious effect of magnesium stearate. The results suggest that surfactant alone does not affect drug dissolution, but that it interacts with magnesium stearate during powder mixing. This interaction would reduce the net surface coverage of the drug-excipients by magnesium stearate. Furthermore, the water-soluble hydrophilic surfactant would help to detach any magnesium stearate film covering the drug-excipients, thus alleviating the decrease in drug dissolution caused by magnesium stearate. On the other hand, lipophilic surfactant is not soluble and ineffective despite its interaction with magnesium stearate.