AFM study of hydrophilicity on acetaminophen crystals.

Pharmaceutical powder processing is notoriously subject to unpredictable jamming, sticking and charging disturbances. To unveil the material science underlying these effects, we use atomic force microscopy (AFM) on a common pharmaceutical, acetaminophen (APAP). Specifically, we study surface adhesion and morphology as a function of relative humidity (RH) for monoclinic acetaminophen, using both plain AFM tips and tips functionalized to be hydrophobic or hydrophilic. Results indicate that the (001) crystal face exhibits significantly higher adhesion (surface potential) than the other crystal faces. For all the faces clear peaks in adhesion occur at 50-60% RH when they are examined using hydrophilic tips. The surface morphology of some facets showed a strong dependence on RH while others showed little or no significant change. In particular, the morphology of the (1-10) faces developed large terraces at high humidity, possibly due to deliquescence followed by recrystallization. These results confirm the hypothesis that different crystal facets exhibit distinct surface potentials and morphology that change with environmental exposure. The work suggests that future studies of powder behaviors would benefit from a more detailed modeling of crystal surface contact mechanics.

Practical methods for improving flow properties of active pharmaceutical ingredients.

OBJECTIVE: The essential aim of this article is to develop effective methods for improving the flow properties of active pharmaceutical ingredients (APIs) without requiring particle size or shape modification. METHODS: The 'formulation' approach used here focuses on enhancing flow properties of three chemically different drug powders (micronized acetaminophen, levalbuterol tartrate, and didesmethylsibutramine tartrate) by using small amounts of lubricants, glidants, and other additives, both individually and in combination. Additives are intimately mixed using a laboratory-scale V-blender with an intensifier bar. Flow index, dilation, and electrical impedance were measured for a total of 24 blends. RESULTS: The flow behavior of all three APIs improved with the addition of these additives. Relative effectiveness of different additive combinations displayed remarkable consistency for all three APIs. Simultaneous presence of SiO2, MgSt, and talc led to substantial decreases in cohesiveness, causing major improvements in flowability of powder. All three properties showed a very tight correlation. CONCLUSIONS: Drug powders with improved flow were found to exhibit low dilation and low impedance values. A common linear correlation between flow index and impedance and also between dilation and impedance was observed for all three APIs, indicating that electric properties play a substantial role in the cohesivity of all three APIs, and suggesting the presence of a common mechanism for the emergence (and mitigation) of cohesive phenomena.

Use of a static eliminator to improve powder flow.

Glidants and lubricants have long been used to improve the flow and processing of pharmaceutical and other powder blends. In this letter, we find that similar improvements can be attained, without additives, by using a simple static eliminator. These results indicate, first, that electrostatic effects on powder blends may be a significant cause of powder aggregation and flow instabilities, and second, that common additives such as magnesium stearate, colloidal silica, and talc may have as their chief effect the reduction of static. This suggests both that intelligent placement of static eliminators can eliminate the need for some of these additives and that judicious engineering of ionic and cationic additives may be effective in improving flow of "clingy" materials.