**3.4 Effectiveness of plasticizers**

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 interactions (Felton, 2007).

Three factors determine the effectiveness of a plasticizer to be used with polymers (Harper, 2006):


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


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

Plasticizers in Transdermal Drug Delivery Systems 99

Glycerine Propylene Glycol

Dibutyl Phtalate Triethyl citrate

Polyethylene Glycol

Triacetin

polymers they are used with are given as a table (Table 3).

polymer films to be used in transdermal drug delivery systems:

formulations.

Reducing the brittleness

Felton, 2007; Rao & Diwan, 1997).

 Improving flow Ensuring flexibility

Table 2. The chemical formulas of the frequently used plasticizers in transdermal

Among the plasticizers commonly used in the formulation of transdermal films, there are the phthalate and citrate esters and glycol derivatives (Gal & Nussinovitch, 2009). The plasticizers used in the studies conducted through last 20 years, their proportions and the

Following are the reasons which can be counted among those for adding plasticizers to the

Enhancing the resistance and tear strength of the polymer film (Bergo & Sobral, 2007;

plasticizer are DSC analyses and the decrease in glass transition temperature when plasticizer is added to polymer (Felton, 2007; Zhu et al., 2002).

In pharmaceutical formulations, effectiveness of a plasticizer agent substantially depends on its amount added to the formulation and on the polymer-plasticizer interaction. When an aqueous dispersion is in question, the proportion and amount of partition was found to be dependent on the solubility of the plasticizer in water and its affinity to the polymer phase. When water-insoluble plasticizers will be dispersed in an aqueous medium, they should firstly be emulsified and then added to the polymer (Felton, 2007).
