**3. Plasticizers**

Plasticizers are generally non-volatile organic liquids or solids with low melting temperature and when added to polymers, they cause changes in definite physical and mechanical characteristics of the material (Bharkatiya et al, 2010; Felton, 2007; Gooch, 2010; Meier et al., 2004).

### **3.1 The role of plasticizers in pharmaceutical formulations**

The main reasons of adding plasticizers to polymers, improving flexibility and processability are counted (Harper, 2006; Höfer & Hinrichs, 2010; Rahman & Brazel, 2004; Whelan, 1994). Upon addition of plasticizer, flexibilities of polymer macromolecules or

Plasticizers in Transdermal Drug Delivery Systems 97

Tendency to migration, exudation, evaporation or volatilization of the plasticizers employed

Other properties expected from an ideal plasticizer are its workability, its ability to provide desired thermal-electrical and mechanical characteristics to the end product, its durability at high and low temperature values, its being effective over a wide temperature range and not being affected by ultraviolet radiation, its cost being low and its conformance to the health

While some of approximately 600 commercial plasticizers are very effective in softening the polymers, the others do not exhibit efficiency in this area and are used for different purposes (Harper, 2006). To exhibit efficiency, the plasticizer should be able to transit from solvent phase to polymer phase and then it can diffuse into polymer and disrupt the intermolecular

Three factors determine the effectiveness of a plasticizer to be used with polymers (Harper,

1. A flexible plasticizer molecule with long (CH2)n chains is more effective in increasing

2. Low polarity and hydrogen bonding cause decrease in the interaction between the

3. The plasticizers with low molecular weight are more active and they increase the

The forces affecting the polymer-plasticizer mixtures are identified as hydrogen bonds, dipole-dipole interactions and dispersion forces. The methods used in measuring the extent

Plasticizers are generally compared with a plasticizer with well known characteristics such as dioctylphthalate. A characteristic such as modulus or hardness is chosen and a value for this characteristic is determined. The ratio of plasticizer concentrations (test/dioctylphthalate) required to achieve this value is defined as the effectiveness of the plasticizer (Whelan, 1994). The effectiveness can also be measured by graphing the modulus versus plasticizer concentration and the graphs of various plasticizers can be compared (Harper, 2006). Most commonly used methods in measuring the effectiveness of the

in a polymeric system must be low (Felton, 2007; Harper, 2006).

polymer and the plasticizer (borderline compatibility).

of polymer plasticizer interaction can be listed as follows (Felton, 2007):

and safety arrangements (Rahman & Brazel, 2004).

**3.4 Effectiveness of plasticizers** 

interactions (Felton, 2007).

the polymer flexibility.

flexibility more.

 Torsion braid pendulum Vapor pressure depression

Gas-liquid chromatography

 Nuclear magnetic resonance (NMR) Spectroscopy Fourier Transform Infrared (FTIR) Spectrometry

Melting point depression

 Osmotic pressure Swelling tests

Viscometry

2006):

macromolecular segments increase as a result of loosening of tightness of intermolecular forces (Bergo & Sobral, 2007; Höfer & Hinrichs, 2010).

The plasticizers with lower molecular weight have more molecules per unit weight compared to the plasticizers with higher molecular weight. These molecules can more easily penetrate between the polymer chains of the film forming agent and can interact with the specific functional groups of the polymer (Gal & Nussinovitch, 2009).

By adding plasticizer to a polymeric material, elongation at break, toughness and flexibility are expected to increase, on the other hand tensile stress, hardness, electrostatic chargeability, Youngs modulus and glass transition temperature are expected to decrease (Gal & Nussinovitch, 2009; Harper, 2006; Rahman & Brazel, 2004).

Plasticizers with low molecular weight, act by reducing the secondary bonds (e.g. hydrogen bond) of the polymer chains and themselves forming secondary bonds (Gal & Nussinovitch, 2009). While low molecular weight improves miscibility with the polymer, the second factor increasing the compatibility is the realization of strong mutual hydrogen bonding (Harper, 2006). Thus, weakening of interaction of the polymer chains decrease tensile strength and glass transition temperature and so the flexibility of polymer films increases (Felton, 2007; Rahman & Brazel, 2004).
