9. Preformulation
• It is defined as the phase of research and
development in which preformulation studies
characterize physical and chemical properties
of a drug molecule in order to develop safe,
effective and stable dosage form.
10. OBJECTIVES
• To establish the physico-chemical parameters of a
new drug entity.
• To determine its kinetics and stability.
• To establish its compatibility with common
excipients.
• It provides insights into how drug products should be
processed and stored to ensure their quality.
12. BULK CHARACTERIZATION
Crystallinity
• Crystal habit & internal structure of drug can affect
bulk & physicochemical property of molecule.
• Crystal habit is description of outer appearance of
crystal.
• Internal structure is molecular arrangement within
the solid.
• Change with internal structure usually alters crystal
habit. Eg. Conversion of sodium salt to its free acid
form produce both change in internal structure &
crystal habit.
14. Different shapes of crystals
• Depending on internal structure compounds is classified as
• 1. Crystalline
• 2. Amorphous
• Crystalline compounds are characterized by repetitious
spacing of constituent atom or molecule in three dimensional
array.
• In amorphous form atom or molecule are randomly placed.
• Solubility & dissolution rate are greater for amorphous form
than crystalline, as amorphous form has higher thermodynamic
energy.
• Eg. Amorphous form of Novobiocin is well absorbed whereas
crystalline form results in poor absorption.
15. • In amorphous and crystalline forms, a solid drug may be anhydrous or a
solvate/hydrate.
• When a solid form contains a solvent, it is known as a solvate.
16. • Polymorphs differ from each other with respect to
their physical property such as
• Solubility
• Melting point
• Density
• Hardness
• Compression characteristic
• Eg. Chloromphenicol exist in A,B & C forms, of
these B form is more stable & most preferable.
17. ANALYTICAL METHODS FOR THE
CHARACTERIZATION OF SOLID FORMS
• Microscopy
• Hot stage microscopy
• Thermal analysis
• X-ray diffraction
• Infrared (IR) spectroscopy
• Proton magnetic resonance (PMR)
• Nuclear magnetic resonance (NMR)
• Scanning electron microscopy (SEM)
18. PARTICLE SIZE
• Particle size is characterized using these terms :
• Very coarse, Coarse, Moderately coarse, Fine ,Very
fine .
• Particle size can influence variety of important factor
like:
- Dissolution rate
- Uniform distribution
20. SOLUBILITY STUDIES
• The equilibrium solubility is based on the phase-
solubility technique proposed by Higuchi-Connors
Method
• Drug dispersed in solvent in a closed container
agitated at a constant temperature using shakers then
clarified by centrifugation and the supernatant can be
assayed by HPLC, UV, GC ,etc after filteration.
21.
22. pKa determination
• pKa is the dissociation constant of a drug
• The un-ionized drug is lipid soluble thus permeates
through lipid membrane.
• The ionized substance is lipid insoluble therefore
permeation is slow.
• Degree of ionization depends on pH
23. POWDER FLOW PROPERTIES
• Powder flow properties can be affected by
change in particle size, shape & density.
• The flow properties depend on:
1. Force of friction.
2. Cohesion between one particle to another.
• Fine particle posses poor flow by filling void
spaces between larger particles causing packing &
densification of particles.
• By using glident we can alter the flow properties.
e.g. Talc
25. Determination of Powder Flow
Properties
• By determining Angle of Repose.
• A greater angle of repose indicate poor flow.
• It should be less than 30°. & can be determined by following
equation.
tan θ = h/r.
where, θ = angle of repose.
h=height of pile.
r= radius.
26. Determination of Powder Flow
Properties
• Measurement of free flowing powder by
compressibility of powder.
• Also known as Carr's index.
• Where Vb bulk volume and Vt is tapped volume
• It is simple, fast & popular method of predicting
powder flow characteristics.
