Sinhgad Technical Education Society’s
Sinhgad institute of pharmacy narhe, Pune 3/17/2023
Presented by –
Mr. Pavan B. Zalte
1st year M. Pharm
Prof. Supriya Nikam
Department of pharmaceutics
Investigation of physical, chemical and mechanical properties of drug
molecule in order to develop safe, effective, and stable dosage form.
This information may dictate many of subsequent event & approaches
in formulation development. This first learning phase is called as
To establish the physicochemical parameters of 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 endure their quality
• Colour, odour, taste of the drug must be recorded
COLOUR ODOUR TASTE
white Pungent Acidic
Cream yellow Sulphurous Bitter
tan Fruity Bland
shiny Aromatic Intense
• A crystalline particle is characterized by definite external and internal
• Crystal habit - external shape of a crystal
• Polymorphic state - refers to the definite arrangement of molecules
inside the crystal lattice.
• During crystallization, molecule may arrange themselves in various
geometric configurations, resulting in distinct packing arrangement or
orientation in crystal structure.
Amorphous drug has atoms or molecules randomly placed (without definite
structure) within them. The amorphous form is of higher thermodynamic
energy, greater solubility as well a higher dissolution rate than the
corresponding crystalline form.
It is the ability of the compound to crystallize as more than one distinct
crystalline species with different internal lattice.
Polymorphs are of 2 type
The polymorph which can be reversibly changed from one form into another
by varying temp or pressure is called as enantiotropic polymorph.
Polymorph which is unstable at all temperature & pressure is called as
Monotropic polymorph. Eg. Glyceryl stearate.
Polymorphs differ from each other with respect to their physical
property such as
• Melting point
• Compression characteristic
Eg. Chloromphenicol exist in A,B & C forms, of these B form is more
Stable & most preferable. 3/17/2023 12
Methods for analysing polymorphs
• Optical crystallography
• DSC (Differential Scanning Calorimetry)
• TGA (Thermogravimetric Analysis)
• XRD (X Ray Diffraction)
• IR (Infra Red)
• SEM (Scanning Electron Microscopy) 3/17/2023 13
• Many drug substances have tendency to adsorb atmospheric moisture.
• Hygroscopicity classified into four classes:
1. Slightly hygroscopic: increase in weight is >0.2%w/w & <2%w/w
2. Hygroscopic: increase in weight is >2%w/w & <15%w/w
3. Very hygroscopic : increase in weight is >15%w/w.
4. Deliquescent : Sufficient water is adsorbed to form solution
Change in moisture level can influence
• Chemical stability
• Compactibility 3/17/2023 14
• A volume of powder is filled into a glass cylinder and repeatedly
tapped for a known duration.
• The volume of powder after tapping is measure.
Bulk density = weight/ bulk volume
Tapped density = weight/ true volume
• Carr’s compressibility index
Hausner ratio and flow
Flow character Hausner ratio
Very poor 1.46-1.59
Very Hauser poor >1.60
The angle of repose
• The maximum angle which is formed between the surface of pile of powder and
horizontal surface is called the angle of repose.
tan θ = h / r
h = height of pile
r = radius of base of pile
Descriptive term Parts of solvent required for 1
part of solute
Very soluble <1
Freely soluble 1 to 10
soluble 10 to 30
Sparingly soluble 30 to 100
slightly solube 100 to 1000
Very slightly soluble 1000 to 10000
Practically insoluble or insoluble 10000 and over
• Solubility and absorbtion can altered by changing pH
• The Henderson -Hasselbach equation provides an estimate of the ionized
and unionized durg concentration at a particular pH.
For acidic compounds,
pH = pKa + log (un-ionized drug) / [ionized drug]
for basic compounds,
pH = pKa + log (ionized drug) / [un-ionized drug]
Ionization constant- pKa
• For very weakly acidic drug (pKa >8) such as phenytoin and ethosuximide,
or for very weakly basic drugs, (pKa<5), such as diazepam the unionized
form is present throughout the GIT and there absorption is rapid.
• For weakly acidic drug (pKa= 3-7), such as aspirin and ibuprofen, the
unionized form is present within the acidic contents of the stomach, but the
drug is ionized in intestinal media. Such drugs are better absorbed from
• For weakly basic drug (pKa=5-8), such as morphine and choroquine the
unionized form is present within the basic content of the intestine, but drug
is ionized in acidic media of stomach. Such drug are better absorbed from
• For strongly acidic drugs, such as cromolyn sodium or strongly basic drugs
such as erythromycin ,the ionized form is in both the stomach and intestine.
An incompatibility in the dosage form can result in any of the
following changes :
Changes in dissolution
An increase in
• Dissolution of drug particle is controlled by following factors:
• The ratio of unionized drugs dispersed between the organic (n-octanol) and
aqueous (water) phases at equilibrium is known as the partition coefficient
• This is helpful to predict drugs’ ability to cross cell membrane.
Partition coefficient =0 drug equally soluble in water and organic solvent
Partition coefficient >1 = drug is lipophilic
Partition coefficient <1 = drug is hydrophilic
The primary objective of this study is investigation and identification of stable
storage condition for drug in the solid state and identification of compatible
excipients for a formulation.
Types of stability Conditions
the shelf life of
Chemical Retains its chemical
Physical Retains appearance,
Threapeutic effect Drug action remains
• Preformulation study helps to develop safe, effective and stable dosage form.
• Preformulation has an impact on the selection of the drug candidate,
formulation components, physicochemical properties of drug.
• Preformulation studies focus on the physicochemical properties of new
compound that could affect the drug performance.
• Preformulation study also focus on the stability and solubility of drug
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pharmaceutical new drug molecule and products: an overview. The american
journal of pharmacy. 2013;1(3):1-20.
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and development of new drug molecules. International J. Of pharmaceutical
science and research. 2016 june 1;7(6):2313-0
3. Hasan MM, Al Habib S, islam MM, Islam MM, Karim MS, Banik K, Rashid
HA. Pharmaceutical preformulation for product development & analytical
techniques use in new dosage form. International journal of pharmacy &
4. Leon lachman / Lieberman’s , The theory and practice of Industrial Pharmacy .
Indian 4rth edition CBS publisher, reprint 2020, page no.217-251
5. Michael E Aulton, Pharmaceutics- The design and manufacture of medicines, 3rd
International edition, page no. 23-24
6. Remington, Pharmaceutics- The science and practice of pharmacy, Volume 1, 20th edition,
Page no. 705.
7. D. M. Brahmankar and Sunil B. Jaiswal, Biopharmaceutics and Pharmacokinetics- a
treatise, Vallabh Prakashan, Page no. 27-29.