**7. Plasticized polymeric microparticles**

It is possible to differentiate two types of microparticles on the basis of their supramolecular texture. Microcapsules consist of a central part, which is called the core, and the peripheral part called the wall. The core contains the active ingredient; the wall is composed of the polymer. The microspheres are composed of a blend of a polymer and a suspended or dissolved active ingredient in the whole volume. The purpose of plasticization of polymers as the carriers of active ingredients in the microparticles is the modification of the kinetics of release either by changes in their hydrophilicity or lipophilicity, or a change in the Tg value, or a change in crystallinity. Release of active substances connected with these parameters of polymeric materials, and can be influenced by swelling, erosion, desorption, obstructive phenomena, osmotic phenomena, capillarity, etc.

Microspheres from the blends of hydroxypropyl methylcellulose and ethylcellulose with metoprolol were plasticized with diethyl phthalate. With increasing concentration of the active ingredient, the velocity of release was decreased. Microparticles plasticized in a 5% concentration of the hydrophobic excipient possessed the velocity of release identical with that of the non-plasticized microspheres, an increase of the concentration of the plasticizer from 15 % to 20 % resulted in a significant increase in the velocity of release (Somwanshi et al., 2011). Indomethacin-loaded microspheres from poly(methyl methacrylate) intended for oral administration were prepared. The period of release of the active ingredient from non-plasticized microparticles was 8 h. After addition of triacetin, the release lasted for 24 h. Fourier transform infrared and nuclear magnetic resonance spectra demonstrated an interaction of the hydrogen type bonds between indomethacin and the polymer. No interaction was demonstrated between triacetin and indomethacin or the polymer (Yuksel et al., 2011).

The liquid pharmaceutical formulations for oral administration with modified release of active principle, excluding amoxicillin was patented. Microcapsules prepared by microencapsulation of the active ingredient using proper polymer-plasticizer mixture were homogeneously dispersed into the external liquid phase (Castan et. al, 2011).

In the course of release, the microspheres from poly(DL-lactide) were plasticized with water from the dissolution medium. Tg values rapidly decreased. At temperatures higher than Tg a rapid erosion of microspheres occurred, whereas at lower temperatures the polymer did not change for the period of the experiment (Aso et al., 1994). The microspheres from poly(L-

ISFI of this type use the protected name Alzamer® Depot technology (Alza Corporation) and are intended for subcutaneous administration. Thanks to the hydrophobic plasticizer, the systems possess a lower speed of degradation with a smaller burst and a slower release of the active ingredient (Matschke et al., 2002). Biocompatibility of plasticizers is higher than in the case of hydrophilic solvents. The advantage of most plasticizers of this type is their low volatility. Proteins and peptides are not dissolved in the systems, their suspensions are chemically very stable (Solanki et al., 2010). For a sufficiently decreased miscibility of ISFI of this type with the surrounding tissue liquid it is necessary to have the solubility of plasticizers in water lower than 7 % (Brodbeck et al., 2000). In situ forming thin membranes were prepared by mixing poly(lactide-co-glycolide) with 10 % polysorbate 80 as the

It is possible to differentiate two types of microparticles on the basis of their supramolecular texture. Microcapsules consist of a central part, which is called the core, and the peripheral part called the wall. The core contains the active ingredient; the wall is composed of the polymer. The microspheres are composed of a blend of a polymer and a suspended or dissolved active ingredient in the whole volume. The purpose of plasticization of polymers as the carriers of active ingredients in the microparticles is the modification of the kinetics of release either by changes in their hydrophilicity or lipophilicity, or a change in the Tg value, or a change in crystallinity. Release of active substances connected with these parameters of polymeric materials, and can be influenced by swelling, erosion, desorption, obstructive

Microspheres from the blends of hydroxypropyl methylcellulose and ethylcellulose with metoprolol were plasticized with diethyl phthalate. With increasing concentration of the active ingredient, the velocity of release was decreased. Microparticles plasticized in a 5% concentration of the hydrophobic excipient possessed the velocity of release identical with that of the non-plasticized microspheres, an increase of the concentration of the plasticizer from 15 % to 20 % resulted in a significant increase in the velocity of release (Somwanshi et al., 2011). Indomethacin-loaded microspheres from poly(methyl methacrylate) intended for oral administration were prepared. The period of release of the active ingredient from non-plasticized microparticles was 8 h. After addition of triacetin, the release lasted for 24 h. Fourier transform infrared and nuclear magnetic resonance spectra demonstrated an interaction of the hydrogen type bonds between indomethacin and the polymer. No interaction was demonstrated between triacetin and indomethacin or the

The liquid pharmaceutical formulations for oral administration with modified release of active principle, excluding amoxicillin was patented. Microcapsules prepared by microencapsulation of the active ingredient using proper polymer-plasticizer mixture were

In the course of release, the microspheres from poly(DL-lactide) were plasticized with water from the dissolution medium. Tg values rapidly decreased. At temperatures higher than Tg a rapid erosion of microspheres occurred, whereas at lower temperatures the polymer did not change for the period of the experiment (Aso et al., 1994). The microspheres from poly(L-

homogeneously dispersed into the external liquid phase (Castan et. al, 2011).

plasticizer (Koocheki et al., 2011).

polymer (Yuksel et al., 2011).

**7. Plasticized polymeric microparticles** 

phenomena, osmotic phenomena, capillarity, etc.

lactide) and poly(lactide-co-glycolide) were obtained. After preparation using a standard solvent evaporation technique after freeze and oven drying these microparticles contained up to 3 % of water. Residual water markedly decreases Tg values according to Gordon-Taylor relationship (Passerini & Craig, 2001).

The microspheres intended for target oriented drug distribution were prepared from poly(lactic-co-glycolic acid) containing the chemotherapeutic agent etoposide in various concentrations. Plasticization with tricaprin in concentrations of 25 % and 50 % significantly increases the velocity of etoposide release in comparison with the microspheres without a plasticizer (Schaefer & Singh, 2002). The microcapsules containing the active ingredients soluble in water were prepared by the o/o/o emulsion method under the extraction of the solvent. Peanut oil was employed in the middle oily phase of multiple emulsion (Elkharraz et al., 2011). This peanut oil plasticized the internal phase containing a solution of the active ingredient and poly(DL-lactide) or poly(lactide-co-glycolide) .

The velocity of release of the anticancer agent paclitaxel from poly(lactic-co-glycolic) microspheres was increased after addition of 30 % of isopropyl myristate, 70 % of the active ingredient was released within 3 weeks. After an increase in the concentration of the plasticizer to 50 % there was another increase in the velocity of the process. The plasticizer did not influence the course of degradation of polymers. Release of paclitaxel took place by the mechanism of diffusion from minimatrices (Sato et al., 1996). Analogous conclusions were published in a similar case of microspheres with etoposide (Schaefer & Singh, 2000).

*In situ* forming microparticle systems are based on the emulsification of the solution of the active ingredient and polymer in the outer oily or aqueous phase. After the application of the emulsion there occurs separation of the solvent to the biological environment and solidification of the system. Besides water-soluble solvents it is possible to use the more hydrophobic, in a limited degree water soluble ones, which act as plasticizers. Myotoxicity of the plasticizers of this type is lower; the following series of decreasing toxicity was found: benzylalcohol > triethyl citrate > triacetin > propylene carbonate > ethyl acetate. Myotoxicity of ethyl acetate was comparable with the isotonic sodium chloride (Rungseevijitprapa et al., 2008).
