**9. Conclusion**

The plasticization of polymers used in pharmaceutical technology can solve a lot of problems during the dosage forms formulation and can improve the quality of the final polymeric drug delivery system. The processing disadvantages can be thus overcome, or even a new technology can be enabled. The products of new quality are obtained by film coating of tablet with the thin layer of a plasticized polymer. The conventional film coating polymers mask the unpleasant organoleptic qualities of drug incorporated within the solid dosage form and protect the active drug substance from exposure to light, atmospheric moisture and oxygen. The functional coating polymers are used to modify the drug release profile, including the delayed release and sustained release. The membranes plasticized with suitable additive reaches the optimal parameters of permeability combined with the required drug release profile. Thanks to significant decrease of viscosity using the plasticizers, the *in situ* forming implants can be formulated and administered by an injection needle or a trocar. Multiparticulate dosage forms after incorporation of the proper plasticizer dispose of increased bioavailability.

Plasticized polymers play the unsubstitutable role in the formulation of the bioadhesive drug delivery systems. The adhesive properties were revealed in plasticized star-like branched terpolymers of dipentaeythritol, D,L-lactic acid and glycolic acid. The multifunctional plasticizers methyl salicylate, ethyl salicylate, hexyl salicylate, and ethyl pyruvate can serve not only as plasticizers, but potentially also as pharmacodynamic efficient ingredients. In accordance with the spreading theory of bioadhesion, the decrease in viscosity resulted in improving of the bioadhesivity after addition of these plasticizers.

Fig. 2. Relation between viscosity and adhesivity of the branched oligoester carriers plasticized by various type and concentration of the plasticizers (triethyl citrate (TEC),

The plasticization of polymers used in pharmaceutical technology can solve a lot of problems during the dosage forms formulation and can improve the quality of the final polymeric drug delivery system. The processing disadvantages can be thus overcome, or even a new technology can be enabled. The products of new quality are obtained by film coating of tablet with the thin layer of a plasticized polymer. The conventional film coating polymers mask the unpleasant organoleptic qualities of drug incorporated within the solid dosage form and protect the active drug substance from exposure to light, atmospheric moisture and oxygen. The functional coating polymers are used to modify the drug release profile, including the delayed release and sustained release. The membranes plasticized with suitable additive reaches the optimal parameters of permeability combined with the required drug release profile. Thanks to significant decrease of viscosity using the plasticizers, the *in situ* forming implants can be formulated and administered by an injection needle or a trocar. Multiparticulate dosage forms after incorporation of the proper

Plasticized polymers play the unsubstitutable role in the formulation of the bioadhesive drug delivery systems. The adhesive properties were revealed in plasticized star-like branched terpolymers of dipentaeythritol, D,L-lactic acid and glycolic acid. The multifunctional plasticizers methyl salicylate, ethyl salicylate, hexyl salicylate, and ethyl pyruvate can serve not only as plasticizers, but potentially also as pharmacodynamic efficient ingredients. In accordance with the spreading theory of bioadhesion, the decrease in viscosity resulted in improving of the bioadhesivity after addition of these plasticizers.

methyl salicylate (MS), ethyl salicylate (ES).

plasticizer dispose of increased bioavailability.

**9. Conclusion** 


Pharmaceutical Applications of Plasticized Polymers 85

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**10. References** 

1520-5762



### **10. References**

84 Recent Advances in Plasticizers

triethyl citrate, tributyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, glycerol, ethylene glycol,

oligoesters or low-molecular polyesters, polyesteramides, PEGs, polypropylene glycol, blend of triacetin and oligomeric

active ingredients (ibuprofen, theophylline, salts of metoprolol

triethyl citrate, methyl salicylate, ethyl salicylate, hexyl salicylate,

tributyl citrate, triacetin, PEG 200, secondary plasticizer (propylene glycol, diethyl phthalate, oleic acid)

water (relative humidity), citric acid monohydrate, active ingredients

particulate systems

free membranes polymeric matrices *in situ* forming systems microparticles

bioadhesive drug delivery systems

moisture protection and odor/taste masking coatings bioadhesive drug delivery systems

time-controlled drug

polymeric matrices

polymeric membranes for transdermal

microparticles intraocular lenses hard contact lenses

*in situ* implants

release

system

propylene glycol, PEGs

poly(1,3-butanediol),

and chlorpheniramine), ethanol, polysorbate 80, water, tricaprin, peanut oil,

isopropyl myristate

(metoprolol tartrate, chlorpheniramine maleate), auxiliary compounds (surfactants, preservatives- methylparaben, solvents, cosolvents, desolvating

and coacervating agents)

dioxide, dibutyl phthalate

colloidal dispersion of PVA) triethyl citrate polymeric matrices

benzyl alcohol, benzyl benzoate, ethyl heptanoate, propylene carbonate, triacetin, triethyl citrate

Poly(methyl methacrylate) Triacetin, supercritical carbon

Table 2. List of plasticized polymers reviewed in presented chapter.

polyvinylpyrrolidon glycerol, PEG 200 or 400

ethyl pyruvate

**polymer Plasticizer Applied as** 

**Pharmaceutically used** 

Whey protein Sunflower protein

Poly(lactic acid)

Star-like branched terpolymers

esters ammoniated (Eudragit® E grades)

Poly(lactide-co-glycolide)

of dipentaeythritol, D,L-lactic acid and glycolic acids

Copolymers of methacrylate

Copolymers of ethyl acrylate and methyl methacrylate (Eudragit® RL and RS grades)

Blend of polyvinyl alcohol and

Kollicoat SR30D (aqueous

Various non-soluble polymers


Pharmaceutical Applications of Plasticized Polymers 87

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**5** 

*Turkey* 

**Plasticizers in Transdermal** 

Sevgi Güngör, M. Sedef Erdal and Yldz Özsoy

*Department of Pharmaceutical Technology, Beyazt- Istanbul* 

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

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

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

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

**1. Introduction** 

et.al., 2001).

backing layer (Walters and Brain, 2007).

systems (Quan, 2011).

**Drug Delivery Systems** 

*Istanbul University Faculty of Pharmacy* 

