1. Complex Formation
Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D
Department of Pharmaceutics
Faculty of Pharmacy
Omer Al-Mukhtar University
Tobruk, Libya.
E-mail: nanjwadebk@gmail.com
2014/03/16 1
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

2. CONTENTS
1. Definition
2. Metal Complex
3. Organic Molecular Complex
4. Inclusion Complex
5. Methods of Analysis
6. Continuous variation
7. Spectroscopy methods
8. Distribution methods
9. Protein Binding
10. Drug Action
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Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

3. Definition
• Complex compounds are defined as those
molecules in which most of the bonding
structures can be described by classical
theories of valency between atoms, but one or
more of these bonds are somewhat
anomalous(different).
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4. Metal Complex
• In this type, metal ion constitutes the central atom
(substrate) and interacts with a base (electron-pair
donor, ligand).
• This type of interaction leads to the formation of
coordination bonds between the species.
Classification of metal complex
1. Inorganic types
2. Chelates
3. Olefin types
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5. 1. Inorganic types
• In inorganic metal complexes, the ligand provides
only one site for binding with metal.
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6. 2. Chelates
• Chelates are a group of metal ion complexes in which
a substance (ligand) provides two or more donor
groups to combine with a metal ion.
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EDTA: Ethylenediamine tetraacetic acid

7. 3. Olefin types
• These types of complexes are used as catalysts
in the manufacture of bulk drugs,
intermediates and in the analysis of drugs.
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8. Organic Molecular Complex
• In this type of coordination complexes, components
are organic molecules and these are held together by
weaker forces or hydrogen bonding.
Classification of organic molecular complex
1. Drug and caffeine complexes
2. Polymer types
3. Picric acid types
4. Quinhydrone types
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9. 1. Drug and caffeine complexes
• Drugs such as benzocaine, procaine and tetracaine
form complexes with caffeine.
• A number of acidic drugs are known to form
complexes with caffeine.
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Tobruk, Libya.

10. 2. Polymer types
• Many pharmaceutical additives such as polyethylene
glycols (PEGs), carboxymethyl cellulose (CMC)
contain nucleophilic oxygen. These can form
complexes with various drugs.
E.g. Polymers: carbowaxes, pluronics etc.
Drugs: tannic acid, salicylic acid, phenols etc.
Carboxyl methylcellulose (CMC) + Amphetamine =
poorly absorbed complex (tablet additive – drug
interaction)
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11. 3. Picric acid types
• Picric acid, being a strong acid, forms organic
molecular complexes with weak bases, whereas it
combines with strong bases (anesthetic activity of
butesin) to yield salts.
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12. 4. Quinhydrone types
• The molecular complex of this type is obtained by
mixing alcoholic solutions of equimolar quantities of
hydroquinone and benzoquinone.
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13. Inclusion Complex
• These complexes are also called occlusion
compounds in which one of the components is
trapped in the open lattice or cage like crystal
structure of the other.
Classifications of Inclusion complex
1. Channel types
2. Layer types
3. Clathrates
4. Monomolecular types
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14. 1. Channel types
• Channels are formed by crystallization of the host
molecules, the guest component is usually limited to
long, unbranched straight chain compounds.
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15. 2. Layer types
• Compounds such as clays, montomorillorite
(constituent of bentonite), can entrap hydrocarbons,
alcohols and glycols.
• They form alternate monomolecular (monoatomic)
layers of guest and host.
• Their uses are currently quite limited; however these
may be useful for catalysis on account of a larger
surface area.
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16. 3. Clathrates
• It is available as white crystalline powder, during
crystallization, certain substances form a cage-like
lattice in which the coordinating compound is
entrapped.
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17. 4. Monomolecular types
• Monomolecular inclusion compounds involve the entrapment
of a single guest molecule in the cavity of one host molecule.
• Most of the host molecules are cyclodextrins.
• The interior of the cavity is relatively hydrophobic, whereas
the entrance of the cavity is hydrophilic in nature.
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18. Methods of Analysis
• The analysis of complexes involves the estimation of
two parameters.
1. The stoichiometric ratio of ligand-to-metal or donor-
to-acceptor.
2. Stability constant of the complex.
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19. Methods of Analysis
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20. Continuous variation
• The physical properties, such as dielectric constant,
refractive index and spectrophotometric extinction
coefficient, are characteristics of a particular species.
• When there is no complexation between these species
(A and B), the value of property is additive.
• This particular behaviour is represented in figure as
dotted line. In case of complexation, these properties
change, i.e. additive phenomena do not hold good.
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21. Continuous variation
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22. Spectroscopy methods
• The UV spectroscopy is used extensively in
determining rate constants, equilibrium constants,
acid-base dissociation constants etc for chemical
reactions.
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23. Distribution methods
• The distribution behaviour of a solute between two
immiscible liquids is expressed by distribution
coefficient or partition coefficient.
• When a solute complexes with an added substance,
the solute distribution pattern changes depending on
the nature of a complex.
• A set of such experiments provides data for the
estimation of complex equilibrium stability.
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24. Protein Binding
• The phenomenon of complex formation with proteins
is called as protein binding of drugs.
Protein binding may be divided into:
1. Intracellular binding: These receptors with which
drug interact to show response are called as primary
receptors.
2. Extracellular binding: These receptors are called
secondary or silent receptors.
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25. Equilibrium Dialysis Method
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26. Dynamic Dialysis Method
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27. Drug Action
• Protein binding inactivates the drug, because
sufficient concentration of drug cannot be built up in
the receptor site for action. Example is
naphthoquinones.
• Certain drugs though bind to proteins, still retain the
drug activity. Examples are penicillins and
sulfadiazine.
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Tobruk, Libya.

28. References
• Text book of Physical Pharmaceutics by Dr.
CVS Subrahmanyam.
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University, Tobruk, Libya.

29. THANK YOUe-mail: nanjwadebk@gmail.com
2014/03/16
Faculty of Pharmacy, Omer Al-Mukhtar
University, Tobruk, Libya.
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