**1. Introduction**

90 Recent Advances in Plasticizers

Udipi, K. & Cheng, P. (2004). Plasticized stent coatings. US Pat. Appl. No. 0215336 (October

Warren, S.L., Dadey, E., Dunn, R.L., Downing, J.M. & Li, E.Q. (2009). Sustained delivery

Warren, S.L., Osborne, D.W. & Holl, R. (2008). Adhesive bioerodible ocular drug delivery

Winzenburg, G., Schmidt, C., Fuchs, S. & Kissel, T. (2004). Biodegradable polymers and their

*Pharmaceutics,* Vol.404, No.1-2 (February 2011), pp. 102-109, ISSN 0378-5173 Zhu, Y., Shah, N.H., Malick, A.W., Infeld, M.H. & McGinity, J.W. (2002). Solid-state

*Delivery Reviews*, Vol.56, (February 2004), pp. 1453-1466, ISSN 0169-409X Yuksel, N., Baykara, M., Shirinzade, H. & Suzen, S. (2011). Investigation of triacetin effect on

system. US Pat. Appl. No. 20080268021 (October 30, 2008)

formulations of octreotide compounds. US Pat. Appl. No. 20090092650 (April 09,

potential use in parenteral veterinary drug delivery systems. *Advanced Drug* 

indomethacin release from poly(methyl methacrylate) microspheres: Evaluation of interactions using FT-IR and NMR spectroscopies. *International Journal of* 

plasticization of an acrylic polymer with chlorpheniramine maleate and triethyl citrate. *International Journal of Pharmaceutics, Vol.* 241, No.2, (July 2002) pp. 301–310,

28, 2004)

2009)

ISSN 0378-5173

Transdermal delivery is one of the non-invasive methods for drug administration. Patient compliance is improved and continuous, sustained release of drug is achieved by following the application of transdermal formulation on the skin (Guy 1996; Tanner & Marks 2008). Transdermal drug delivery systems, known as patches, are dosage forms designed to deliver a therapeutically effective amount of drug across a patient's skin in a predetermined time and controlled rate (Aulton 2007; Tiwary et.al., 2007; Vasil'ev et.al., 2001).

Transdermal drug delivery systems can be divided into three main groups : a) adhesive systems, in which the drug in adhesive, b) matrix type systems in which the drug in a matrix polymer and c) reservoir systems (Delgado-Charro & Guy 2001; Williams, 2003). Although there are differences in the design of transdermal therapeutic systems, several features are common to all systems including the release liner, the pressure sensitive adhesive, and the backing layer (Walters and Brain, 2007).

There are three critical considerations in the selection of a transdermal drug delivery system: adhesion to skin, compatibility with skin, and physical or chemical stability of total formulation and components (Walters and Brain, 2007). The adhesive nature of the patches is critical to the safety, efficacy, and quality of the product. Therefore the three important performance tests to monitor adhesive performance of patches are tack, shear strength and peel adhesion (Gutschke et al., 2010; Patel and Baria 2011; Ren et al., 2009). The choice and design of polymers, adhesives, penetration enhancers and plasticizers in transdermal patches are also critical because they have a strong effect on drug release, permeability, stability, elasticity, and wearing properties of transdermal drug delivery systems (Quan, 2011).

Plasticizers are low molecular weight resins or liquids, which cause a reduction in polymerpolymer chain secondary bonding, forming secondary bonds with the polymer chains instead (Gal and Nussinovitch, 2009; Rajan et al., 2010). The reasons for the use of plasticizers in transdermal drug delivery systems are the improvement of film forming properties and the appearance of the film, decreasing the glass transition temperature of the

Plasticizers in Transdermal Drug Delivery Systems 93

Fig. 1. Schematic representation of transdermal patch types: A. Reservoir, B. Matrix,

a. **Reservoir Systems:** In these systems, the drug is in a reservoir as liquid. Drug molecules are contained in the storage part, as a suspension in a viscous liquid or dissolved in a solvent. In the second type, there is a membrane made of a polymer with different structure, which separates the reservoir from the adhesive layer. In these systems, the membrane controls the release rate of the drug. The membrane can be porous or nonporous. The adhesive polymer on the exterior surface of the membrane enables the transdermal to adhere to skin. In these systems, drug release rate can be controlled by membrane thickness and adhesive layer (Delgado-Charro & Guy 2001;

Transderm-Nitro (Nitroglycerin), Transderm-Scop (Scopolamine), Catapress-TTS (Clonidine), Estraderm (Estradiol) can be given as examples to the commercially available

C. Drug-in-Adhesive transdermal systems.

Padula et.al. 2007; Williams, 2003).

membrane diffusion controlled systems.

polymer, preventing film cracking, increasing film flexibility and obtaining desirable mechanical properties (Wypych, 2004). One of the many advantages of plasticizers used in transdermal formulations is the controlling of the release rate of therapeutic compound which can be done by the selection of the plasticizer type and the optimization of its concentration in the formulation. The commonly used plasticizers in transdermal patches include phthalate esters, phosphate esters, fatty acid esters and glycol derivatives (Bharkatiya et al, 2010; Wypych, 2004).

The objectives of this chapter are to summarize the compositions and types of the transdermal drug delivery systems; to emphasize the role and effectiveness of plasticizers in transdermal drug delivery systems and to cover the research studies and current developments related to the development of transdermal formulations.
