A concentric cylinder shear device for the study of stability in intravenous emulsions.
This paper introduces the use of a concentric cylinder shear device for studying the stability of intravenous emulsions under shear, and examines the relationship between shearing conditions and the emulsion droplet size and distribution, as characterised by laser diffraction and optical counting. Theoretically, the device generated flow in the Taylor region, but a linear relationship between the natural log mean droplet diameter and time, which was observed at all shear rates, suggested that coalescence kinetics could be treated in a manner analogous to laminar flow. An order of magnitude increase in coalescence rate was achieved within the shear rate range examined (2802-6164 s(-1)), yet irrespective of shear rate, the particle size distribution evolved a similar multi-peak pattern with common secondary peaks at 1.8 and 3.8 microm. This pattern was similar to that observed during shake testing of the emulsion. In emulsions destabilised with increasing concentrations of NaCl, a shear-dependent threshold was observed above which there was a marked increase in coalescence. This threshold behaviour also occurred on shake testing, and it appears to be analogous to the critical coagulation concentration observed when shear testing of suspension. The concentric cylinder device allows a variable shear rate to be applied in a precise and controlled way and therefore represents an advance over shake testing. Emulsions of differing stability may be examined, and the technique has application in the study of emulsion behaviour and stability under shear, and potentially in accelerated stability studies.
Han
Jihong
J
Formulation Insights Group, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Washington
Clive
C
Melia
Colin D
CD
D000465:Algorithms; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry*; D007262:Infusions, Intravenous; D007700:Kinetics; D010316:Particle Size; D033081:Shear Strength; D012965:Sodium Chloride / Q000737:chemistry; D013314:Stress, Mechanical; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods*
D004655:Emulsions; D012965:Sodium Chloride