ABSTRACT
In this article the gravitational displacement rheometer (GDR) is used to characterize the effects of formulation composition and environmental conditions (moisture) on flow properties of cohesive pharmaceutical powders under unconfined conditions. The amount of moisture in the sample often has important effects on the physical and chemical properties of pharmaceutical solids. Properties such as flow, compaction, disintegration, dissolution, hardness and chemical stability are all influenced by moisture. In the case of lactose, as moisture content increases in the powder bed, the flowability becomes poorer as the moisture condenses on the surface and increases cohesion. The celluloses show opposite effect as compared to lactose. Here, as moisture content increases, the flow properties improve dramatically. The GDR also captures the effect of lubricant concentration on the cohesion of powders. The presence of lubricant does not play any significant impact for free flowing powders, but as powder cohesion increases, the lubricants allow for improved flowability of powders. The GDR was also used for a case study of real drug formulation. The methodology was able to evaluate the impact of humidity and lubricant concentration on the flow properties of the formulation.
Subject(s)
Cellulose/chemistry , Excipients/chemistry , Powders/chemistry , Rheology/methods , Stearic Acids/chemistry , Chemical Phenomena , Chemistry, Physical , Drug Stability , Hardness , Humidity , Lactose , Lubrication , Rheology/instrumentation , Solubility , Surface Properties , Technology, PharmaceuticalABSTRACT
A new technique to quantify the effects of shear intensity and total shear on the homogeneity, flowability and bulk density of a lubricated free-flowing pharmaceutical blend and on properties of resulting tablets is presented. A modified Couette cylindrical cell with uniformly spaced pins is used to create a uniform shear environment. The range of lubricant concentrations explored is 0-2% (on a mass basis). Sheared blends are used to produce tablets in the Presster (a simulator of an actual tablet press), allowing us to correlate the shear history of the blend (shear intensity and total shear) with the crushing hardness of tablets. The results show that the larger the total shear, the more homogeneous the blend. Bulk density increases with total shear until reaching a distinctive plateau. Results also indicate that high total shear affects the blend flow properties. For tablets, crushing hardness decreases as concentration of lubricant and total shear increase. Interestingly, and unexpectedly, under constant total shear, shear intensity affects the crushing hardness of tablets only slightly.
