Drug Targeting Organ-Specific Strategies

68 3 Pulmonary Drug Delivery: Delivery To and Through the Lung
Table 3.4. Major properties of powders to be determined during pre–formulation and some of the
methods to be used.
Powder property Method
• Particle size and size distribution • Cascade impactor analysis
Wet or dry laser diffraction analysis
Microscopy
Coulter counter analysis
Sieve analysis
Sedimentation analysis
Time of flight measurements
(Scanning electron) microscopy
• Particle surface area, shape and • Scanning electron microscopy
texture (morphology) Atomic force microscopy
Particle flow (e.g. angle of repose)
BET measurements
• Moisture sorption and desorption • Dynamic gravimetric sorption (DVS)
• Surface energy • Contact angle measurements
Isothermal microcalorimetry
Gravimetric sorption
Inverse gas chromatography
• Crystallinity and crystal form • Differential scanning calorimetry
Thermogravimetric analysis
Isothermal microcalorimetry
Infra red analysis
X–ray diffraction
Sorption and desorption measurements
(DVS)
• Solubility and dissolution rate
• Partition coefficient
• Stability in dry state and in solution
• Impurities
tem. Staniforth [61] gave an overview of the required pre-formulation tests for dry powder
formulation development.The nature of the surface (e.g. surface morphology, crystallinity or
surface energy) of the particles is of utmost importance and should be studied in detail. Two
reviews [62,63] described a number of methods for characterizing particle morphology.
Table 3.4 summarizes the major properties of powders which need to be characterized in
pre-formulation. The effect of micronization (or other high energy processes), which is often
applied to the powder (surface), should also be investigated as this may alter the properties
of the powder during processing [64].This may also alter the performance of the formulation.
Different dry powder formulations for inhalation were recently reviewed [53,65]. Spherical
pellets or adhesive mixtures are the most used formulation principles in dry powder inhaler
systems (see Figure 3.3). Spherical pellets consist of the pure micronized drug or the
micronized drug combined with a micronized excipient such as lactose or glucose. The small
drug particles are formulated into the large spherical pellets to improve processing properties
such as flowability and precision of metering. The pellets should be strong enough to
withstand the filling process as well as normal handling and shock as may occur during use by
the patient. On the other hand, it should be taken into account that optimal lung deposition