**1.1. Using poly- and oligo-saccharides for drug delivery; Possibility for mechanochemical synthesis of supramolecular systems**

Providing efficient ways of delivering active drug molecules to their destinations in target organisms, the so-called drug delivery, is among major challenges in today's pharmacy. An important relevant issue is to enhance the efficacy and safety of pharmaceutical compounds by correcting their solubility [1-3]. Polysaccharides (e.g., derivatives of cellulose, chitosan, and alginic and hyaluronic acids) make part of compositions with controlled or retarded drug release [4-6], while oligosaccharides (alpha-, beta-, and gamma-cyclodextrins and their derivatives) are broadly used to increase solubility and dissolution rates as they can form guest-host supramolecular complexes with poorly soluble drugs [7, 8]. Until recently little was known whether complexes of this kind may result from the activity of natural plantderived or synthetic water-soluble polysaccharides though these are common elements in dietary supplements or drugs. Polysaccharides have aroused no interest in this respect, possibly because the technology for producing supramolecular complexes requires liquid phases (solutions or melts): The complexes form by molecular interaction in the liquid, and the solid phase is extracted then on drying (solutions) or cooling (melts). However, being easily soluble in water, polysaccharides are almost insoluble in other solvents and, moreover, decompose on heating rather than melt. The target drugs, instead, often dissolve rapidly in non-aqueous solvents but are poorly soluble or insoluble in water. Therefore, the liquid-phase synthesis of polysaccharide-drug complexes has been impeded by the lack of co-solubility.

© 2012 Dushkinet al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

This difficulty may be surmountable with solid-state chemistry approaches, specifically, with mechanochemical transformations in mixtures of solids [9-11]. Unlike the liquid-phase synthesis, mechanochemical treatment is a simpler single-stage process going without solvents or melts and respective additional procedures. The flow chart in Fig. 1 shows a simplified sequence of transformations the powder mixtures experience during dry milling in various mills.

There may be three types of main products relevant to our study, depending on the properties of starting materials:


In fact, they all are solid dispersions that form supramolecular structures (complexes or micelles) that enclose drug molecules and provide their solubility.

Generally, solid-phase processes have a number of advantages in laboratory and technological uses as they yield, in a shorter time, materials which the classical liquid-phase technology can never provide and allow avoiding problems associated with melts or solvents and side reactions. The high potentiality of mechanical activation was proven in our previous studies [12-14], e.g., on quick-dissolving pharmaceutical compositions [15-18] and synthesis of polyfluorinated aromatic compounds [19, 20].

In this synopsis we present techniques for synthesizing supramolecular complexes of poorly soluble drugs with water-soluble polysaccharides or with glycyrrhizic acid (a plant-derived glycoside), describe physicochemical properties of their solid forms and solutions, and report the results of pharmacological testing.

**Figure 1.** Mechanochemical transformations in mixtures of solids organic substances.
