**3.1 Effect of solubility parameters of the plasticizer on drug release**

The physicochemical properties, particularly the solubility parameters of the plasticizer and extent of the plasticizer leaching act the major role in the drug release from a plasticized polymer system. The differences in the drug release patterns are observed in the case of using either lipophilic or hydrophilic plasticizers. The lipophilic plasticizers, (e. g. dibutyl sebacate) are shown to remain within the polymeric system upon exposure to the release media, assuring integral and mechanically resistant coatings during drug release. In contrast, hydrophilic plasticizers leached out of the system, resulting either in decreased mechanical resistance and thus cracking, or in facilitated pore formation. As drug release was controlled by diffusion through the intact membrane and/or water-filled cracks (with significantly different diffusion coefficients), the mechanical stability of the polymeric system and the onset of crack formation are of major importance for the resulting drug release profiles.

### **3.2 Effect of affinity of the plasticizer to the polymer on drug release**

Furthermore, the affinity of the plasticizer to the polymer is found to be decisive. The plasticizer redistribution within the polymeric systems during coating, curing and/or storage affects the drug release rate. For instance, dibutyl sebacate has a higher affinity to ethycellulose than to Eudragit RL, resulting in potential redistributions of this plasticizer within the polymeric systems and changes in the release profiles. Importantly, adequate preparation techniques for the coating dispersions and appropriate curing conditions could avoid these effects, providing stable formulations (Bodmeier & Paeratakul, 1997).

#### **3.3 Effect of plasticizer concentration on drug release**

The plasticizer concentration has a significant impact on the drug release of a diffusioncontrolled drug delivery system. Low concentrations of the plasticizer often result in an

The release profile of the drug from degradable matrices is typically triphasic. The three phases can be summarized by an initial rapid drug release (burst effect) from the matrix surface, followed by a phase where the incorporated drug diffuses more slowly out of the inner bulk matrix and then, the remaining drug release phase due to bulk degradation of the polymer. The extent of the initial burst release can be controlled by plasticizers. High burst release can be minimized by hydrophobic plasticizers; the opposite effect is achieved by

Biodegradation rate and thus the release of incorporated drugs depend on the polymer molecular weight parameters. Low molecular weight polymers or oligomers are preferred as drug carriers, as their hydrolysis may proceed simultaneously or just somewhat slower than drug release. A low molecular weight poly(D,L-lactic) acid with a linear molecule constitution is not suitable as a carrier due to a lag-time. Star-like copolymers of hydroxy acids with polyhydric alcohols, such as pentaerythritol, mannitol, glucose, polyvinyl alcohol and others are particularly advantageous. These branched carriers unlike the linear are endowed with low gyration radius (Kissel et al. 1991). Drug release from this type of carriers can be modified not only by molecular weight, but also more significantly by the degree of

The physicochemical properties, particularly the solubility parameters of the plasticizer and extent of the plasticizer leaching act the major role in the drug release from a plasticized polymer system. The differences in the drug release patterns are observed in the case of using either lipophilic or hydrophilic plasticizers. The lipophilic plasticizers, (e. g. dibutyl sebacate) are shown to remain within the polymeric system upon exposure to the release media, assuring integral and mechanically resistant coatings during drug release. In contrast, hydrophilic plasticizers leached out of the system, resulting either in decreased mechanical resistance and thus cracking, or in facilitated pore formation. As drug release was controlled by diffusion through the intact membrane and/or water-filled cracks (with significantly different diffusion coefficients), the mechanical stability of the polymeric system and the onset of crack formation are of major importance for the resulting drug

Furthermore, the affinity of the plasticizer to the polymer is found to be decisive. The plasticizer redistribution within the polymeric systems during coating, curing and/or storage affects the drug release rate. For instance, dibutyl sebacate has a higher affinity to ethycellulose than to Eudragit RL, resulting in potential redistributions of this plasticizer within the polymeric systems and changes in the release profiles. Importantly, adequate preparation techniques for the coating dispersions and appropriate curing conditions could

The plasticizer concentration has a significant impact on the drug release of a diffusioncontrolled drug delivery system. Low concentrations of the plasticizer often result in an

hydrophilic plasticizers, which leach out of polymer in the hydrophilic medium.

**3.1 Effect of solubility parameters of the plasticizer on drug release** 

**3.2 Effect of affinity of the plasticizer to the polymer on drug release** 

avoid these effects, providing stable formulations (Bodmeier & Paeratakul, 1997).

**3.3 Effect of plasticizer concentration on drug release** 

their branching (Pistel et al., 2001).

release profiles.

increase in the rigidity of the polymer instead of the expected softening effect. This effect, known as antiplasticization*,* can be used as a formulation strategy which can modulate drug permeability of polymers used in pharmaceutical systems.

The antiplasticizing effect of water on the transport properties of disintegration controlled systems such as tablets is highly relevant during the manufacturing, handling and storage of the product; water does not antiplasticize during drug release. Once in the body, pharmaceutical formulations are subjected to a water saturated environment. Consequently, water will act exclusively as a plasticizer under such conditions (Chamarthy & Pinal, 2007).

The theophylline release profile from soluble starch plasticized with sorbitol exhibits two valleys, which can be explained as a simultaneous plasticizing effect of water penetrating from the dissolution medium and the antiplasticizing effect of sorbitol contained in the formulation (Chamarthy & Pinal, 2008).

Antiplasticization can be expected to significantly affect drug release and thus a factor that has to be taken into consideration in formulation development.
