2. Preformulation Study
Preformulation study; the term is frequently hear
d in a pharmaceutical industry. But, what is it exa
ctly?
A Preformulation study is an investigation of the
physical, chemical, and mechanical properties of
a drug substance to develop a safe, effective, and
stable dosage form. Thus, it forms an integral part
of the drug development process.
3. To establish the physicochemical properties of the
new drug substance
To determine its kinetic profile and stability
To determine its compatibility with inactive ingred
ients or excipients
To know the methods of drug processing and stora
ge
Just like any research study is carried out to
accomplish a particular goal, the main objective of
Preformulation studies is to accomplish the
following:
4. In order to accomplish these
goals, certain Preformulation
parameters of the drug substance a
re investigated. Let’s see what
these parameters are:
5. 1.Organoleptic properties
of the drug
Organoleptic properties are the aspects that
can be experienced through one’s senses like
taste, smell, sight, and touch.
Thus, it includes a recording of the colour,
odour, and taste of the drug.
6. 2.Bulk characters of the
drug
• This includes:
Crystallinity and Polymorphism
Hygroscopicity
Fine particle characterization
Powder flow properties
7. Crystallinity and Polymorphism
Crystallinity refers to the outer appearance
and internal structure of the drug molecule
and can affect its physicochemical
properties.
Polymorphism is the ability of a
compound to crystallise in different shapes
with different internal structure.
8. Hygroscopicity
Hygroscopicity is the measure of the
tendency to adsorb atmospheric moisture by
the drug substance.
It characterizes the drug stability with
respect to the environmental humidity.
9. Fine particle characterization
The size of the drug particle can influence its
dissolution rate, suspendability and other
properties.
Thus, it becomes important to classify the
drug substances as coarse, moderately coarse,
very coarse, fine, and very fine.
10. Powder flow properties
Since the majority of active pharmaceutical in
gredients are delivered as powders, either as a
pill or for dissolution, understanding and
controlling the powder behaviour of drugs are
extremely important.
Powder flow properties help you understand
the ease with which the drug powder will flow
under a set of specific conditions like humidity,
pressure etc.
11. 3.Solubility analysis
Ionization constant- pKa is the measurement of the
acidity of the compound. Its determination helps in un
derstanding the solubility, protein binding, and permea
bility of the drug substance to characterize its propertie
s like absorption, distribution, metabolism and excretio
n from the body.
pH solubility profile helps to understand the influ
ence of pH on drug solubility, stability, and absorption.
Common ion effect (Ksp) determines the solubili
ty of the drug substance when a soluble compound hav
ing a common ion with the drug is added to the test sol
ution.
12. Thermal effects help to evaluate the drug solubility
with respect to the changes in the temperature of the solve
nt.
Solubilization is the method of increasing the solubili
ty of sparingly soluble drug substance by various techniqu
es like adding a co-solvent, changing the pH and temperat
ure, adding a surfactant, reducing the particle size etc.
Partition co-efficient is the measurement of the dru
g lipophilicity or ability to cross a cell membrane.
Dissolution is the process of resolving the drug substa
nce into its individual components and characterizing thei
r properties.
13. 4.Stability analysis
Stability in toxicology formulations
Solution stability
pH-rate profile
Solid state stability
Bulk stability
Compatibility
The stability of the drug is studied with respect to
various factors like:
14. Thus, by investigating the above
parameters of a new drug molecule
, scientists can formulate the drug
substance into a stable, safe, and
effective dosage form that can be
easily taken by the patient to cure
his illness.
