This document discusses the physical and chemical factors that affect drug kinetics and properties. It covers various bulk characteristics like crystallinity, polymorphism, hygroscopicity and particle size. It also discusses methods to determine properties like surface area, ionization constant, hardness, friability and dissolution. Finally, it covers various chemical reactions and factors like oxidation, hydrolysis, photolysis, racemization, polymerization, and isomerization that can impact drug stability. Understanding these physical and chemical properties is important for pre-formulation studies and developing stable drug formulations.

1. 
Presented by
M.Ramasudha
M.Phrmacy 1st year
2018MPH40A021

2.  INTRODUCTION
 PHYSICAL FACTORS
 CHEMICAL FACTORS
 CONCLUSION
 REFERENCES

3.  Physical and chemical reactions involved in the formation of
or changes in the structures of atoms and molecules and their
interaction affecting the drug kinetics.
 Investigation of physical and chemical properties of a drug
substance –alone and or when combined with excipients is
crucial during pre-formulation studies.

4.  Bulk characteristics :
1.Crystallinity:
Crystal habit (i.e. outer appearance of the crystal)and the
internal structure (i.e molecular arrangement within the solid )
can affect physicochemical property of the drug

5. Internal structure
Crystalline Amorphous
• Molecules are arranged in 3D
• Prepared by slow
precipitation
• Low thermodynamic energy
so ,low solubility rate
• Molecules are randomly
arranged
• Prepared by rapid precipitation
• Higher thermodynamic energy
so higher solubility rate

6. 2. Polymorphism
Compound may be amorphous or crystalline where the
compound has more than one crystalline form it is said to be
exhibit polymorphism
 Thermodynamically stable at a given temperature and
pressure
 The stable polymorph exhibits the highest melting point ,
lowest solubility , and maximum chemical stability
Eg :diamond and graphite
 Polymorphism is exhibited in diamonds and graphite. Both
diamond and graphite are polymorph of the same element
carbon

7.  Both the elements entirely consist of carbon but they have
different crystalline structures and physical properties , since the
structure determines the properties of the compounds.

8. 3. Hygroscopicity
It is tendency of material to absorb moisture from atmosphere and
dynamic equilibrium with water in the atmosphere
Some drugs have the tendency to absorb atmospheric moisture
 The amount of absorbed moisture depends upon the
o Atmospheric humidity
o Temperature
o Surface area
o The mechanism for the moisture uptake
 The changes in moisture level greatly influences the chemical
stability, flow ability, compactability

9.  Method of determination:
carry out study , sample of compound are accurately weighed into
container and placed at various humid condition for period of up to
2weeks.
If weight gain-deliquescent or hygroscopic
If weight loss – efflorescent
Effect of Hygroscopicity:
 Effects of flow property
 It affects compaction
 Important in aerosol.
 Effects chemical stability

10. Particle size:
 It affects the bulk flow , formulation homogeneity of the drug
particles
 In case of tablets , sizes and shape influence the flow and
mixing efficiency of powders and granules.
 Size can also be a factor in stability
 Fine materials are relatively more open to attack from
atmospheric oxygen , the humidity , and interacting excipient
than are coarse materials

11.  General techniques for determining particle
size:
 Optical microscopy
 Polarizing microscope
 Scanning electron microscope(SEM)
 Transmitted x-ray beam
 Polarizing microscope is used to determine whether a
compound is crystalline or amorphous.

12. Surface area:
 Particle size and surface area of a solid drugs are inversely
related
Two types of surface areas :
 Absolute surface area :
Which is the total area of solid surface of any particle .
 Effective surface area :
Which is the area of solid surface exposed to the dissolution
medium

13. Ionization constant:
A constant that depends upon the equilibrium between the ions and
the molecules that are not ionized in a solution or liquid.
The Henderson- Hasselbalch equation provides an estimate of the
ionized and unionized drug concentration at a particular pH.
 For acidic compounds:
pH = pKa + log (ionized drug)/(un ionized)
 For basic compounds
pH= pKa + log (unionize drug)/(ionized drug)

14.  Compression force:
The compressional force increases , the tablet hardness
increases and the friability decreases . A certain amount of
compression force required to produce a tablet that passes the
friability specifications . However , if too high compression
Force is applied ,it may not lead to an appreciable
Increase in hardness but could adversely affect the dissolution
of the tablet and may also cause internal stress cracks ,leading to
tableting defects.

15. Hardness :
 The resistance of tablets to capping, aberation or breakage
under conditions of storage, transportation and handling
before usage depends on its hardness
 If tablet is too soft it may not be able to withstand handling
during subsequent processing such as coating or packing and
shipping operations.
 The tablet hardness has been associated with tablet property
such as density and porosity.

16. Friability :
 Friability is defined as the percent of weight loss by tablets
due to mechanical action during the test.
 Friability is closely related to tablet hardness and is designed
to evaluate the ability of tablet to with stand aberration in
packing , handling and shipping.
 Minimum weight loss of the tablet should not be NMT 1%
 There should not be any broken tablet.

17. Dissolution :
 Active absorption of oral dosage forms depends on
adequate release of the API from the product.
 Dissolution or solubility of the API plays a vital role in this
aspect.
 Dissolution testing is used as tool to identify crucial effect
in the bioavailability of the API.

18. Chemical properties:
1) Oxidation:
It is very common pathway for drug degradation in both liquid and
solid formulation.
 Oxidation is the gain of oxygen , loss of hydrogen and /or loss of
electrons
 When iron reacts with oxygen with forms a chemical called rust. The
iron is oxidized and the oxygen is reduced
 Oxidation occurs in two ways:
Auto oxidation
Free radical oxidation

19. Factors affecting oxidation process:
1) Oxygen concentration
2) Light
3) Heavy metals particularly those having to or more valance state
4) Hydrogen & hydroxyl ion
5) Temperature
Prevention of oxidation :
1. Reducing oxygen content
2. Storage in a dark and cool condition
3. Addition of chelating agent (Eg : EDTA , citric acid , tartaric acid)
4. Adjustment of pH

20. Hydrolysis :
o It is the cleavage of chemical bonds by the addition of water
o The reaction of water with another chemical compounds to
form two or more products , involving ionization of the
water molecule usually splitting the other compound.
Examples :
o The catalytic conversion of starch to glucose
o Saponification
o The formation of acids or bases from dissolved ions

21. Prevention of hydrolysis:
pH adjustment
o Formulate the drug solution close to its pH optimum stability
o Addition of water miscible solvent information
o Optimum buffer concentration
Addition of surfactant
o Non ionic , cationic, and anionic surfactant stabilizes the
drug against base catalyst

22. Photolysis :
 photo dissociation , or photo decomposition is a chemical
reaction in which a chemical compound is broken down by
photons
 Since a photons energy is inversely proportional to its
wavelength , electromagnetic waves with the energy of
visible light or higher , such as ultra violet , x-rays and
gamma rays are usually involved in such reactions .

23. Prevention of photolysis:
o Suitable packing :
Eg :yellow –green glass gives the best protection in
u.v. region while amber gives considerable protection
against u.v. radiation but little from I.R.
o Protection of drug from light :
Eg : Nifedipine is manufactured under Na light

24. Racemization:
 Racemization is the process in which one of a compound ,
such as an L-amino acid, converts to the other enantiomer.
 The compound then alternates each form while the ratio
between the (+)and (-) groups approaches 1:1, at which
point it becomes optically inactive .
 If the racemization results in a mixture where the enantiomer
are present in equal quantities, the resulting sample is
described as racemeric or a racemate

25. Polymerization :
 Polymerization is a process of reacting monomer molecules
together in a chemical reaction to form polymer chains or three
–dimensional networks.
 It is a continuous reaction between molecules .
 More than one monomer reacts to form a polymer.
 Eg: darkening of glucose solution is due to polymerization of
break down products [5-(hydroxyl methyl)furfural.

26. Isomerization :
Is the process by which one molecule is transformed in to
another molecule which has exactly the same atoms , but the atoms
have a different arrangement
Eg : Tetracycline & its derivatives can undergo reversible
isomerization at pH range 2-6.
Trans – cis isomerization of amphotericin B.

27. Conclusion :
Physicochemical properties are plays a major role for
dosage form stability, safety and effectiveness

28. References :
 Applied Biopharmaceutics and pharmacokinetics by Leon
Shargel
 Physical pharmacy by Martin
 www.google.com