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.
Pingali
Kalyana C
KC
Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 09954, USA.
Saranteas
Kostas
K
Foroughi
Reza
R
Muzzio
Fernando J
FJ
D000082:Acetaminophen / Q000737:chemistry; D000420:Albuterol / Q000737:chemistry; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003102:Colloids; D003503:Cyclobutanes / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D017097:Electric Impedance; D005079:Excipients / Q000737:chemistry*; D010316:Particle Size; D011208:Powders / Q000737:chemistry*; D012212:Rheology / Q000295:instrumentation / Q000379:methods; D012822:Silicon Dioxide / Q000737:chemistry; D013229:Stearic Acids / Q000737:chemistry; D013627:Talc / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*
D003102:Colloids; D003503:Cyclobutanes; D005079:Excipients; D011208:Powders; D013229:Stearic Acids; D013627:Talc; D000082:Acetaminophen; C031183:stearic acid; D012822:Silicon Dioxide; D000420:Albuterol; C058254:sibutramine