Solid State Pharmaceutics

Submitted to-
Dr Shishu
Submitted by-
Tania Pawar
Introduction
Matter comprises of three states namely-
solids,liquids,gases.
They all differ intermolecular , interatomic or ionic
forces
Solid State
Solids are broadly classified into two types-

1.Crystalline Solids

2.Amorphous Solids
Crystalline solids
The solids having definite shape and which are
arranged in an orderly manner.
They show definite melting point and are practically
incompressible.
There are four types of crystalline solids-
1. Ionic crystalline solids
2. Molecular crystalline solids
3. Macromolecular or Covalent networked solids
4. Metallic solids.
Characteristic Molecular Covalent Metallic Ionic crystals
s crystals crystals crystals

Units that molecules atoms Positive ions in Positive and

occupy lattice a sea of negative ions
pts electrons

Binding force Van der wall Shared electons Electrical Electrostatic

and dipole attraction bwt attractions
dipole +ve ions and –
ve electrons

Physical Very soft,low Very hard,highHard or Hard and

properties m.pt,good m.pt,non- soft,moderate brittle,high
insulators conductors to high m.pt,semi
m.pt,good conductors
conductors
examples NH₃,H₂O,CO₂ Diamond,quart Na,Cu,Fe NaCl,KNO₃
z
The various crystals forms are divided into six distinct
crystal systems.
1. Cubic(sodium chloride)
2. Tetragonal(Urea)
3. Hexagonal(iodoform)
4. Rhombic(iodine)
5. Monoclinic(sucrose)
6. Triclinic(boric acid)
7. Trigonal
Crystal system Cell dimensions Crystal angles

Cubic a=b=c α=β=γ=90°

Orthorhombic a≠b≠c α=β=γ=90°

Tetragonal α=b≠c α=β=γ=90°

Monoclinic a≠b≠c α=γ=90°,β≠90°

Triclinic α≠b≠c α≠β≠γ≠90°

Hexagonal α=b≠c α=β=90°,γ=120°

Trigonal α=b=c α=γ=β≠90°

Amorphous solids
Also considered as Non-crystalline solids ,vitreous
solids or supercooled liquids.
It consists of disordered arrangements of molecules.
Hence, does not posses a distinguishable crystal lattice
They are usually isotropic i.e, they exhibit similar
properties in all directions.
Substances such as glass , pitch , and many synthetic
plastics are amorphous solids.
Polymorphs
When a substance exists in more than one crystalline
form , the different forms are designated as
Polymorphs and the phenomena as Polymorphism.
They differ in the arrangement of the molecules in the
crystal lattice.
Polymorphs are of tw0 types-
1. Monotropic polymorphs
2. Enantiotropic polymorphs
Monotropic polymorph-it involves two forms in
which one undergoes an irreversible phase change to
the second form.eg-glyceryl stearate

Enantiotropic polymorphs-Two phases can undergo

a reversible phase transition by altering temperature or
pressure.eg-sulphur
Various polymorphs differ from each other with respect
to their physical properties(but have similar chemical
properties).Different properties are-
1. Melting point
2. Apparent solubility
3. Density and hardness
4. Dissolution characteristics
5. Compression characteristics
6. Optical and electrical properties
7. Vapour pressure
Transition temperature-It is the temperature at
which one form changes to another at a given pressure,
usually 1 atmosphere. At the transition temperature
polymorphs have-
1. Same free energy
2. Identical solubilities
3. Identical vapour pressure
With the help of microscopic observation of samples ,we
can determine transition temperatures.
Below the solid melting temperatures , the polymorph
with the lower free energy , corresponding to the
solubilities or vapor pressure, is the
thermodynamically stable form.
The most direct means for determing transition
temperatures is microscopic observation of samples
held at constant temperature.
Stable and Metastable state
Stable form is the one which is physically more stable
than the other polymorphic forms. Such stable
polymorph represent-
1. Lowest energy state
2. Highest melting point
3. Least aqueous solubility
4. Maximum chemical stability
Metastable forms-The remaining polymorphs are
called metastable forms.They convert to stable forms
with time.They represent
1. Higher energy state
2. Have lower melting point
3. Higher aqueous solubility
4. If kept dry it remains stable for years,therefore
cannot be called unstable form.
 There are various pharmaceutical agents exihibiting
polymorphism.
1. Theobroma oil-used as a suppository base and has
4 polymorphic forms(α,β,γ and β).
2. Sulfameter-antibacterial agent.
3. Tamoxifen citrate-an anti-estrogenic and anti-
neoplastic agent.exists in 2 forms(Α andΒ).
4. Progesterone
5. Carbamazepine.
Crystal habit
The external shape of a crystal is know as crystal
habit.
This is a consequence of the rate at which the different
faces grow.
Changes in the internal packing usually results in the
change in the habit.However, for the same crystal
packing, it is possible to change the external
appearance by changing the crystallisation conditions.
The growth on different faces depend on the relative
affinities of the solute for the solvent and the growing
faces of a crystal.
The external shape can alter the properties of
drugs/excipients.
Crystal habits can cause changes in powder flow,
sedimentation and caking of suspensions.
Different habits of crystals are-
1. Plate
2. Equant or massive
3. Needle or acicular
4. Bladed
5. Tabular
6. Prismatic
Solvates and hydrates
A crystallised compound may contain either a
stoichoimetric or a non-stoichiometric amount of the
crystallisation solvent.
A stoichiometric type of adduct where the solvent
molecules are incorporated in the crystal lattice at
specific sites of the solid are called Solvates and
trapped solvent as solvent of crystallisation.
The solvates can exist in different forms called as
pseuopolymorphs.
When the solvate is associated with the drug is
water,the solvent is known as hydrate.
These are most common solvates form of drug.
The entrapment of water is in exact molar ratio with
the crystallizing material.
Analytical Techniques for characterization of
solid state
Various techniques are available for the investigation
of the solid state.These include-
1. X-Ray diffarction analysis
2. Thermal methods of analysis
3. Microscopial studies
4. Spectro scopic method esp IR
5. dilatometry
X-ray diffraction analysis
It is a unique analytical tool for solid state
pharmaceutical product.
X-ray have been used in the crystal structure studies
in two different ways-
1. Single crystal X-ray crystallography-determination
of bond angles and inter-atomic distances.
2. Powder X-ray diffraction-study of crystal lattice
parameters.
Single crystal X-ray provides the complete
information.However, it is tedious,time consuming
and hence unsuitable for routine use.

Powder X-ray diffraction is both rapid and relatively

simple and is the method of choice.
Thermal analysis
Thermogravimetric analysis(TGA)
It is an effective thermal method useful in the
investigation of polymorphism and in obtaining
pertinent thermodynamic data.
The weight of a sample in a furnace is monitored as a
function of time.
It is an excellent tool to study hydrates.
It can also be used to assess particle size effects and
dehydration or to determine drying conditions for
hydrates.
Differential scanning calorimetry(DSC)
is useful to characterize physical properties of raw
materials, mixtures of materials or finished products.
• A calorimeter measures heat flow into(endothermic)
or out of(exothermic) a material as it undergoes a
phase change and can measure the heat capacity of
material.
Differential thermal analysis(DTA)
Temperature difference between sample and reference is
plotted against time
• Various factors which affect the results are-
temperature difference, resistance to heat flow, nature
of sample and packing of material
• Therefore energies of melting, sublimation and
decomposition cannot be calculated directly.
Microscopical methods
Microscopical methods provide a rapid screening tool
for the characterization of the solid state behaviour.
Various microscopical methods routinely used are-
1. Optical
2. Polarizing
3. Fluorescence
4. Hot stage
Out of the following polarized light microscopy is the
most versatile analytical technique as it is used to
study a wide range of physio-chemical properties on
small quantities of sample
Solid forms can be readily distinguished from each
other by their optical properties, such as refractive
indices,colour,extinction angle and optical dispersion.
It is also used to study variation in crystal
habit,presence of inclusions(solids,liquids,vapour)in
crystals,solubility of crystals in different solvents.
Thermomicroscopy
used to observe thermally induced events(such a
melting point, polymorphic conversions,desolvations
and sublimation)as a small amount of sample is
heated.
Spectroscopic methods
These are useful techniques for characterization of
solid state
NMR,IR,FTIR are mainly used.

These methods require that either the nuclei of the

pair of substances being examined exist in
magnetically inequivalent environment
Dilatometry
Definition: The measurement and study of
dimensional changes in polymers as a function of
temperature, fluid absorption, mechanical stress or
chemical reaction.
The dilation or expansion of a sample confined in a
dialatometer is expressed in terms of specific
volume(ml/g)plotted against time.
Dilactometer is an instrument which measure thermal
expansion or dilation in solids or liquids.
Fats and fatty acid tend to expand when they melt and
to contract,when they pass from a metastable to a
stable polmorphic form.

Eg-Theobroma oil, methyl stearate and

chloramphenicol.