**3.4 Effect of drug-polymer or drug-plasticizer interaction on drug release**

The drug-polymer or drug-plasticizer interaction within the polymer drug delivery system can significantly influence the drug release profile. For instance, when triacetin was added to indomethacin loaded poly(methyl methacrylate) (PMMA) microspheres, a desired drug release profile lasting 24 h was achieved. Originally biphasic release profile, an initial burst effect from the surface of the microspheres followed by a slower drug release phase was surmounted by addition of a plasticizer. There might be a hydrogen bonds formation between the indomethacin hydroxyl group and PMMA, no interaction between triacetin and indomethacin or PMMA as the effects of secondary bonds was observed. The release enhancement of indomethacin from microspheres was attributed to the physical plasticization effect of triacetin on PMMA and, to some extent, the amorphous state of the drug.

The plasticization effect of triacetin on PMMA increased the diffusivity of indomethacin from PMMA. However, this effect was not dependent on the formation of secondary bonds between triacetin and PMMA. This indicates that the triacetin molecules physically separate the PMMA chains by locating within them (Yuksel et al., 2011).

An example of how drug-polymer interaction can affect the drug release can be piroxicamloaded Eudragit E film. The drug-polymer interaction occurring between piroxicam and Eudragit E seems to cause a drag effect, leading to a delay of the piroxicam release from the Eudragit E film (Lin et al., 1995).

Similarly, ibuprofen interacts with the Eudragit RS 30 D polymer through hydrogen bonding, thus ibuprofen acts both as the active ingredient and as the plasticizer for the polymer also. The glass transition temperature of the Eudragit RS 30 D polymer decreased with increasing levels of ibuprofen in the polymeric film. The drug release rate was reduced by increasing the amount of ibuprofen in the polymeric film and by increasing the coating level on the coated beads (Wu & McGinity, 2001).

Pharmaceutically Used Plasticizers 61

Thin films of a thickness of 40 μm from poly(lactide-co-glycolide) containing 10 % paclitaxel were plasticized with polyethylene glycols Mw 8,000 and 35,000 in various concentrations. The plasticizer with a lower molecular mass exerted a great influence on a more rapid release of paclitaxel. Polyethylene glycol was phase separated from copolymer

The active ingredients were demonstrated to act as plasticizers of the polymer. The kinetics of dissolution in phosphate buffer of pH 7.4 and apparent diffusion coefficient including mathematical analysis of data resulted in the expression of the quantitative relationship between the diffusivity of drugs and the initial composition of medicinal substances with a possibility of prediction of the effect of thickness of the membrane and its composition on

Oligoester carrier compound of the equimolar ratio of glycolic acid and lactic acid branched with dipentaerythritol was synthesised by polycondensation (Snejdrova, E. & Dittrich, M.,

The carrier was plasticized using methyl salicylate in concentration of either 10 %, or 20 %, or 30 %. The increase of methyl salicylate concentration in the oligoester matrices influences the aciclovir release *in vitro* in the obvious manner. At 10 % concentration of the plasticizer the 90 % portion of active substance released was achieved after 15 days, at its 20 %

concentration after 9 days , and at 30 % concentration after three days (Fig. 1).

Fig. 1. Acyclovir release from oligoester carrier plasticized by methyl salicylate (MS).

Ethyl salicylate as more hydrophobic plasticizer in comparison to methyl salicylate was used in various concentrations for plasticizing of the oligoester carrier. It influences the aciclovir release kinetics in the more complicated way. The partition coefficient matrix/dissolution medium for drug is in the consequence a character of plasticizer and aqueous medium influx changed. During the drug release process small portion of

Dipentaerythritol

5.0 2,300 16.3

Reactants proportion [weight %] MW [g/mol] Tg [°C]

(Steele et al., 2011).

Lactic acid 47.5

the kinetics of drug release (Siepmann et al., 2006).

2011). Table 3 shows the basic characteristic of the carrier.

Glycolic acid

47.5

Table 3. Relevant characteristics of oligoester carrier.
