

Wednesday, April 26, 2017


Ronak Gajjar
Smt.S.M.Shah Pharmacy College, Ahmedabad
Note: This Material is only Study Purpose only.

Complexation is the combination of individual atom groups, ions or molecules to create one large ion or molecule. One atom or ion is the focal point of the complex. This central atom contains empty electron orbitals that enable bonding with other atoms as well as unshared electrons.
The last stage in complexation involves the sum of individual components' charges. Therefore, there can be zero, negative and positive charges in a complex within a solution. The intermolecular forces involved in the formation of complexes are:
Covalent OR coordinated bonds (Lewis acid-base type)
Van der Waals forces of dispersion
Ion-dipole, dipole-dipole, dipole-induced dipole type
Hydrogen bonding etc.
Complexation behavior is observed in a number of situations in including the handling of dosage form. It is of interest to the pharmacist. The applications of complexation in pharmacy and medicine are enumerated below:
  1. Physical state
  2. Volatility
  3. Solid state stability
  4. Chemical stability
  5. Solubility
  6. Dissolution
  7. Partition coefficient
  8. Absorption and bioavailability
  9. Reduced toxicity
  10. Antidote for metal poisoning
  11. Antibacterial activity
Some complexes are available as drug in market. Like
  1. Povidone-iodine: Polyvinylpyrrolidone (PVP) is a water soluble-polymer and forms a water-soluble complex with iodine. The structure of this complex is:
It is a safe and effective antibacterial and germicidal agent. It is available as a soap for the hand wash of healthcare personnel, surgical hand-scrub and skin preparations. It is also used post-operatively for wound cleaning and protection.

The complexes are classified as follows:
  1. Metal complexes
  1. Inorganic types
  2. Chelates
  3. Olefin types
  4. Aromatic types
  1. Organic molecular complexes
  1. Drug and caffeine complexes
  2. Polymer types
  3. Picric acid types
  4. Quinhydrone types
  1. Inclusion complexes
  1. Channel types
  2. Layer types
  3. Clathrates
  4. Monomolecular types

Inorganic complexes, chelates, olefin complexes and aromatic complexes are included in the metal ion complexes.
Quinhydrone complexes, picric acid complexes, drug complexes and polymer complexes are included in the organic complexes.
Channel lattice complexes, layer type complexes, clatharates, mono and macro molecular complexes are included in the inclusion compounds.
Metal complexes
Inorganic complexes:
Here there will be a metal atom to which the ligands donate the lone pair of electrons. The general ligands are water, ammonia and cyanide molecules.
One point that we have to note is that during the complex formation the lower energy levels like 3d and 4s will be filled earlier to the 4p.
Organic complexes:
The two components are attached by the weak donor acceptor forces. Sometimes the hydrogen bonds may be involved.
The distance in case of organic compounds will be more and so the attraction energy will be less. So the separation of these compounds from the solution is not easy.
Quinhydrone complexes are formed when the alcohol solution of benzoquinone and alcoholic solution of the hydroquinone is mixed in equimolar concentration.
Picric acid complexes are formed when picric acid is treated with weak bases.
Polymeric complexes formed when the polymers have nucleophilic oxygen.
Inclusion complexes:
Channel type: The choleric acids form these type of complexes. The deoxycholeic acid molecules can form channels in which the molecules will get inside.
Layer type: The guest molecule get entrapped with in the layers.
Clatharates: It's a cage like complex. And here there will be no formation of the chemical bonds.
Monomolecular complexes and macromolecular complexes are the inclusion compounds that are classified based on the number of the guest molecules that will get entrapped.

Methods of Analysis
Determination of the stoichiometric ratio of ligand to the metal or donor to the acceptor and a quantitative expression of the stability constant for complex formation are important in the study of complexes. Several methods of estimation of complexes have been developed as follows:
1. Method of continuous variation
2. pH Titration method
3. Distribution Method
4. Solubility Method
5. Spectroscopy and Charge Transfer complexation.
Method of continuous variation: This process uses the estimation of certain additive properties of the complex like dielectric constant, spectrophotometric extinction coefficient etc. According to this process when two components of a complex are mixed and if no interaction occurs between them, then the value of the property is given as the weighted mean of the values of the separate species in the mixture i.e when an additive property is plotted against the mole fraction and if no complexation occurs between the two components then a linear relationship is observed.
pH Titration method: This method is best suitable for complexes when the complex formation is attended by a change in pH.
For example: The chelation of cupric ion with glycine.
Cu2+ + 2NH3+CH2COO-- ====== Cu(NH2CH2COO)2 + 2H+
In the above reaction formation of two protons indicates the decrease in pH occurs with the addition of glycine to a solution containing cupric ions. From the titration curves obtained by plotting pH against the equivalents of base added the increase or decrease in the pH indicates the extent of formation of complex.
Distribution Method: This method says that the distribution of a solute between to immiscible solvents determines the stability constant for certain complexes.
For example: Complexation of iodine with potassium iodide.
Solubility Method: In this method the formation of complexes is based on the solubility of the components in presence of a complexing agent. The excess quantities of drugs are placed in a well-stopper container along with the complexing agent at various concentrations and the bottles are agitated at constant temperature until the equilibrium is attained. Then samples are withdrawn and analysed for complex formation property at different concentrations of the complexing agent.
For example: Complexation of p-aminobenzoic acid by caffeine.
Spectroscopy and Charge Transfer complexation: Absorption spectroscopy both in the visible and U.V region of the spectrum is most commonly used for the analysis of the charge transfer complexes.
Miscellaneous methods: Several other methods are available for the analysis of complexes like NMR and I.R spectroscopy, polarography, circular dicromism, kinetics, X-ray diffraction and electron diffractin.


  • Martin's Physical Pharmacy and Pharmaceutical sciences by Patrick J. Sinko, 5th edition, Lippincott Williams and wilkins publishers, page no 267 to 286.

  • Textbook of Physical Pharmaceutics by C. V. S. Subrahmanyam, 2nd edition, Vallabh Prakashan, page no 275-278




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