**2.1.3 Adhesion of coating influenced by plasticizer**

Good adhesion between a polymer and the surface of a solid is a major prerequisite for the film coating of pharmaceutical dosage forms. Loss of adhesion may reduce the functions that the film-coating provides to the solid substrate, particularly the mechanical protection that the coating ensures to the solid substrate and the drug release modified by coating.

Pharmaceutical Applications of Plasticized Polymers 73

plasticizer redistribution within the polymeric system during coating occurs. As an example can serve pellets coated with blends of ethyl cellulose and Eudragit® L. Dibutyl sebacate used as plasticizer of this coating shows a higher affinity to ethyl cellulose than to

A membrane can be in the form of a free film containing the active ingredient, or it can form the outer wall of the body which is its reservoir together with other excipients. The membrane has a defined thickness; it can be porous or compact, it can contain, in addition to the active ingredient, various excipients including plasticizers. In the case of dosage forms such as buccal and sublingual films, capsules intended for oral, rectal or vaginal administration, and inserts placed into cavities, their membranes and membrane systems possess the function of (1) the primary coating increasing stability and enabling administration, (2) separation from and protection against the influence of the biological

Ethyl cellulose films of standard thickness were prepared by slow evaporation of the solvent from chloroform solutions of a 48.8% ethoxylated cellulose derivative and three plasticizers: classic dibutyl sebacate, vitamin D3 and vitamin E. The individual plasticizers were used in nine different concentrations up to 80 %. It has been demonstrated that primarily αtocopherol (vitamin E) in concentrations of 40 to 50 % is an advantageous and effective plasticizer of ethyl cellulose from the standpoint of toxicity, ultimate strength, toughness, and Young modulus (Kangarlou et al., 2008). Ethyl cellulose of the identical parameters was employed in the preparation of films using the same method, diethyl sebacate in a 40% concentration being used as the plasticizer. Chloroform was evaporated using the standard very slow evaporation procedure. A suitable velocity of stress action was found for the most

Thin films made of poly(lactide-co-glycolide) were prepared from a dichloromethane solution with additions of 15%, 25%, or 50% polyethylene glycol 8 000 and 35 000, yielding potential implants of 40 µm in thickness containing the antitumor drug paclitaxel. Raman spectrometry was used to demonstrate partial separation of the

Soft gelatin capsules were formed by a wall of varying thickness containing about 40 to 45 % of gelatin, which is plasticized with water 20 to 30 % and glycerol, or sorbitol 30 to 35 % (Marques et al., 2009). The plasticizer increased the flexibility of gelatin, with increasing concentration to 45 % it decreased the sensitivity to humidity, decreased the tendency to recrystallization, decreased tensile strength and the elastic modulus, increases elongation

Protein films possess good mechanical properties, but they are very sensitive to atmospheric humidity. Their hygroscopic character can be decreased by adding a hydrophobic plasticizer. Esters derived from citric acid such as triethyl citrate, tributyl citrate, acetyl triethyl citrate and acetyl tributyl citrate were tested in various concentrations (Andreuccetti et al., 2009). Their limited miscibility with an aqueous solution of gelatin was solved by

Eudragit® L (Lecomte et. al., 2004).

plasticizer (Steele et al., 2011).

at break (Bergo & Sobral, 2007).

environment after administration, or (3) controlled release.

conclusive stress-strain deformation diagrams (Sogol & Ismaeil, 2011).

**3. Free membranes** 

There are two substantial forces which influence the polymer adhesion: the strength of the interfacial bonds between the polymeric film and the surface of the solid, and the internal stresses within the film coating. The interfacial bonding between the tablet surface and polymer coating is made primarily with hydrogen bonds, to a lesser extent with dipoledipole and dipole-induced dipole interactions. The addition of plasticizing agents to coating formulations generally decreases the internal stress in the film by decreasing both the elastic modulus and the glass transition temperature of the film coating (Johnson Hathaway, 1991; Rowe, 1981, 1992).

The measured force of adhesion, therefore, would be expected to increase with increased plasticization of the polymer. The contradictory results may be due to the interaction of the plasticizing agent with the polar groups of the polymer within the film structure (Felton McGinity, 1999).

The adhesive property of Eudragit films is effected with organic esters used as plasticizers (triacetin, diethyl phthalate, dibutyl phthalate and tributyl citrate were tested). The molecular weight and solubility parameters of the plasticizer seemed to play an important role in changing the adhesive strength of the Eudragit films. The adhesion of Eudragit films is markedly increased when the concentration of the plasticizer is greater than 25%. Tributyl citrate may be the best choice of the plasticizer for the Eudragit film, particularly for the Eudragit E film.

The molecular weight and solubility parameters of the plasticizer seemed to play an important role in changing the adhesive strength of the Eudragit films (Lina et al., 2000).

The water soluble plasticizers, triethyl citrate and polyethylene glycol 6000, lower the Tg of the films to a greater extent than the hydrophobic plasticizers, tributyl citrate and dibutyl sebacate, and the coatings with the hydrophilic plasticizers exhibit stronger adhesion (Entwistle Rowe, 1979; Felton McGinity, 1997).

The study of the influence of plasticizers on the adhesion of the acrylic polymer to either hydrophilic or hydrophobic tablet compacts revealed that increasing tablet hydrophobicity decreased adhesion of both cellulosic and acrylic polymers (Felton McGinity, 1996, 1997; Rowe, 1977).

### **2.2 Factors negatively influencing the coating**

Polymer-plasticizer incompatibility, plasticizer migration out of polymer (and particularly leaching of plasticizer) as well sticking and aging of the film coated dosage influence not only the mechanical properties, but also drug release (Amighi Moes, 1996; Arwidsson et al., 1991; Bodmeier Paeratakul, 1992; Skultety Sims, 1987). For example, dibutyl sebacate unlike triethyl citrate was found to remain within the polymeric coating upon exposure to the dissolution media and thus mechanical properties of coatings during drug release are maintained. Leaching of triethyl citrate out of the film resulting in decreased mechanical resistances facilitates crack formation.

A blend of polymers can be used in the coating of solid dosage forms, and then the type of plasticizer must be chosen responsibly to ensure good quality of the coating. If the plasticizer has different affinities to the individual polymers forming the blend, the plasticizer redistribution within the polymeric system during coating occurs. As an example can serve pellets coated with blends of ethyl cellulose and Eudragit® L. Dibutyl sebacate used as plasticizer of this coating shows a higher affinity to ethyl cellulose than to Eudragit® L (Lecomte et. al., 2004).
