DOSAGE FORM DESIGN PARAMETERS

SOLID-STATE CHARACTERIZATION AND PHYSICAL BEHAVIOR

Nalini Shastri

SOLID STATE CHARACTERIZATION

BULK LEVEL Micromeritics Solubility Sorption of water Surface properties
Habit Interfacial tension, surface free energy

Mechanical properties
Flow Tensile strength Compactibility

PARTICLE SIZE ANALYSIS

Larger particles irregular shape Diameter or equivalent diameter

DIRECT COMPARISION OF SIZE USING DIFFERENT SIZING TECHNIQUE IS NOT MEANINGFUL

SIZE DETERMINATION METHODS

METHODS CLASSIFIED UNDER

Direct counting Separation Ensemble Misc.

Direct counting techniques

METHOD Optical microscopy UV light microscopy Ultra microscopy SEM TEM (Transmission) Single particle light scattering Electrical zone sensing (Coulter counter) PRINCIPLE Imaging Imaging Imaging Imaging Imaging Electro Magnetic scattering Volume displacement APPLICABLE SIZE RANGE 0.2-100m 0.1-100m 0.01-0.2m 0.001-0.2-10m 0.01-0.5m 0.5-2m 0.4-100-400m

Separation techniques
METHOD Sieving Andreason pipette Gravitational settling chamber PRINCIPLE Size exclusion Sedimentation Gravitation APPLICABLE SIZE RANGE 0.5mm-38m 1-200m >100m

Xray gravitational sedimentation

Optical centrifugal devices X-ray centrifugal sedimentation

Sedimentation
Sedimentation sedimentation

0.5-100m
0.01-5m 0.01-5m

Separation techniques
METHOD Sedimentation field flow fractionation Cyclone separators Cascade impactors PRINCIPLE Sedimentation Size exclusion Sedimentation APPLICABLE SIZE RANGE 0.01-5m >0.5m 0.1-30m

Hydrodynamic chromatography including capillary fractionation Capillary zone electrophoresis

Size exclusion

0.03-1m

Size exclusion

0.03-1m

Ensemble techniques
METHOD
Static light scattering Photon correlation spectroscopy Electrophoretic light scattering Laser diffraction

PRINCIPLE
Electromagnetic wave interaction Electromagnetic wave interaction Electromagnetic wave interaction Electromagnetic wave interaction

APPLICABLE SIZE RANGE 0.05-5m

0.003-2m 0.02-2m 1.2-600m

Miscellaneous techniques
METHOD Small angle neutron scattering (SANS) PRINCIPLE Scattering APPLICABLE SIZE RANGE 0.001-10m

SAXray scattering
Atomic force microscopy Acostic attenuation spectroscopy Gas adsorption (BET) Fisher sub sieve sizer

Scattering
Imaging Spectroscopy Surface area Permeation

0.001-31m

No limits No limits No limits

SIZE DETERMINATION TECHNIQUES - COMPARISION

MICROSCOPY
Optical, polarizing, thermal and chemical Martin diameter Ferret diameter Projected diameter Sample preparation Calibration
Ocular scale + stage micrometer Globe and circle graticule

TYPES OF DIAMETER

1 = Martin 2 = Ferret 3 = Projected

SORPTION TECHNIQUE
Sorption and desorption of water/solvents Water activity Amount of water available for sorption Water activity (Aw) is defined as VP of water divided by VP of pure water at that temperature RH = water activity x 100

SORPTION TECHNIQUE
Samples at different RH/ temp Weight gain Saturated salt solution Labor intensive Equilibrium set up time

Water vapor sorption plot

CRYSTAL HABITS
(Platy)

(Cuboid)

(Rods or prismatic)

(Needle)

PARTICLE SHAPE
SPHERICITY Relation of various diameter Degree of equality of three axes Sphere - minimum SA/unit volume Asymmetric
Difficult to assign meaningful diameter Increases SA/unit volume

PARTICLE SHAPE
Ratio of surface area & Volume factor Wadell sphericity Approximated sphericity Maximum projection sphericity Riley sphericity, YR = (Di/Dc)1/2
Where Di = diameter of largest inscribed circle Dc = Diameter of smallest circumscribing circle

SURFACE AREA
Adsorption method
BET method

Permeability method
Fisher subsieve sizer

DENSITY True density Granule density Bulk density/Fluff density Tap density

TRUE DENSITY
NON POROUS MATERIAL
Liquid displacement Floatation in liquid

POROUS MATERIAL
Gas pycnometry

DERIVED TECHNIQUE
Pressure on powder compact

FLOW PROPERTIES
Shear cell techniques Flow through orifice Angle of repose
Fixed funnel and free standing cone Fixed bed cone Tilting box Carrs index Hausner ratio

FLOW PROPERTIES
CARRS INDEX = rtap - rfluff
x 100

rtap

CARRS INDEX

FLOW

5-15
12-16 18-21 23-35 33-38 >40

Excellent
good Fair to Passable poor V poor V V poor

FLOW PROPERTIES
HAUSNER RATIO = rtap/rfluff

<1.25 good flow; (20% of Carrs index) >1.5 poor flow; (33% of Carrs index) 1.25 1.5; requires addition of glidant

MECHANICAL PROPERTIES
PERMENANT DEFORMATION PRESSURE(H) Stress to cause plastic deformation Pendulum Impact device Rebound height of ball Chordial radius of dent STRESS INTENSITY FACTOR kc Micro indentation device Vicks type

MECHANICAL PROPERTIES
TENSILE STRENGTH (sT) Split die apparatus Square or round compact Permit triaxial decompression Relieves stress in compact uniformly

Compactibility
Densification phenomena First order kinetics Mech of consolidation Identify predominant form of deformation ln [1/(1-D)] = kP + A A = constant related to initial packing k = material related constant = 1/3S
Measure of plasticity of material Greater slope = greater degree of plasticity

ATHY-HECKEL PLOT
Ist slope initial repacking 2nd slope subsequent deformation process Three types are observed