Predicting the properties of solid dosage forms
7
wet-mass consistency, prior to drying, on the ¯ ow proper- pressure above which a material irreversibly deforms;
ties of the dried granules, using the Hausner ratio and strain-rate sensitivity, which describes the eŒect of punch
avalanching behaviour. The Hausner ratio and time be- speed on mean yield pressure; work of compaction, which
tween avalanches of the dried granules decreased with an includes both the plastic compaction energy (recoverable)
increase in wet-mass consistency, indicative of improved and elastic compaction energy (lost) during a particular
granule ¯ ow.
compression event; the compression pressure±tablet tensile
strength relationship ; and elastic recovery of tablets post
compression. Compaction simulators have principally been
used for mechanical property characterisation, for for-
mulation optimisation and prediction of scale-up and for
prediction and selection of suitable compression settings.
During preformulation assessment of a new drug entity
for oral delivery, an understanding of the material’s basic
mechanical properties is required. Nichols & Frampton
E
Powder rheometry. Flow characterisation techniques
have often suŒered through a lack of sensitivity and high
variation between measurements. Powder rheometry
measures the ¯ ow, compaction and cohesion properties of
powders in response to the stresses imposed by a moving
rotor blade (Podczeck 1999a, b).
Podczeck (1999a, b) used powder rheometry to study the
ow and packing properties of diŒerent grades of micro-
(
1998) and Garekani et al (1999) studied the eŒect of
¯
crystal habit on the compression properties of paracetamol.
Polyhedral crystals were more compressible than plate-like
crystals as a result of increased plastic deformation, as seen
by a reduced mean yield pressure and an increase in tablet
tensile strength. Marshall & York (1991) and Sun & Grant
crystalline cellulose. Podczeck (1999b) concluded that, with
appropriate methodology, the powder rheometer was able
to detect small diŒerences in the ¯ ow and packing proper-
ties of microcrystalline cellulose, which could not be
detected from Carr’s index measurements. Podczeck &
Newton (2000) also studied the eŒect of small quantities of
magnesium stearate on the ¯ ow properties of powdered
cellulose using Carr’s index, shear cell and powder rhe-
ometry measurements. Powder rheometry and shear-cell
measurements predicted capsule ®ll-weight uniformity with
greater accuracy than Carr’s index measurements. Powder
rheometry has an advantage over shear-cell methods in
that testing is rapid and simpler to perform. Powder
rheometry has also been used for the study of wet powder
masses. Luukkonen et al (2001) studied the wet-massing
behaviour of microcrystalline cellulose in both a powder
rheometer and a mixer torque rheometer. The powder
rheometer followed a similar torque pattern to mixer torque
rheometry on liquid addition.
(
2001b) showed that plate-like crystals were more com-
pressible than prism-shaped and needle-like crystals for
nitrofurantoin and l-lysine monohydrochloride, respect-
ively. The increase in compressibility was possibly a result
of greater plasticity or a closer packing structure on com-
pression. Sun & Grant (2001a) have also studied the
compaction properties of diŒerent l-lysine salts and found
that tablet tensile strength decreased with increasing yield
strength of the salt. However at high compaction pressures,
tensile strength was determined predominantly by inter-
particle bonding rather than yield pressure.
Compaction simulators may also be used to study the
mechanical properties of excipients. Bolhuis et al (2001)
compared the compaction properties of diŒerent hydrates
of calcium lactate. Calcium lactate pentahydrate was found
to have low strain-rate sensitivity and a high bonding
capacity, indicating its suitability as a ®ller in direct com-
pression formulations. Yang et al (1996) studied the com-
paction properties of polyethylene oxide (PEO) polymers
for controlled-release applications. PEO polymers had low
yield pressures that were highly dependent on punch speed
E
Mercury porosimetry. Guerin et al (1999) attempted to
develop a micro-technique using mercury porosimetry to
characterise ¯ ow behaviour. They concluded that mercury
porosimetry was more sensitive than tap testing and dis-
criminated between powders with similar ¯ ow properties.
(
i.e. high strain-rate sensitivity), suggesting a need to blend
PEO with highly compactable excipients to manufacture
tablets on a high-speed press.
Once characterised, the mechanical properties of both
Tablet compaction and capsule ®lling simulation
E
Tablet machine simulation. The tablet machine (or com-
paction) simulator has considerable bene®ts as a predictive drugs and excipients can be used as input parameters in
technique as it can mimic, in real time, the compression expert systems to predict the most suitable formulation.
cycle of any tablet press and provide a means for character- Characterising the basic mechanical properties of drugs
ising the compaction properties of drugs and formulations and excipients may also aid in setting material speci®cation
using a small quantity of material (Celik & Marshall 1989). limits. Evidence has been provided to suggest that com-
The perceived disadvantage of compaction simulators is paction properties may vary as a function of crystallinity
that they are expensive and studies are often time con- for microcrystalline cellulose (Suzuki & Nakagami 1999)
suming (Celik & Marshall 1989). For a comprehensive and water content for HPMC (Malamataris & Karidas
review on compaction simulation in tabletting research, 1994 ; Nokhodchi et al 1996b, c) and maltodextrin (Li &
the reader should refer to Celik & Marshall (1989) and Peck 1990), indicating the need for control of these
Nokhodchi & Rubinstein (1996).
Jain (1999) reviewed some of the indices that are gener-
materials.
Compaction simulators may be used during formulation
atedusingcompaction simulation tocharacteriseapowder’s optimisation. Asgharnejad & Storey (1996) studied the
compaction and compression properties. In brief, the main eŒect of process and formulation variables on the com-
indices quoted are: mean yield pressure, which is the mean pression properties of an experimental drug using a