**3. Experimental procedures**

398 Biomedical Science, Engineering and Technology

The first stage of drying is called the constant rate period (CRP), because the rate of evaporation per unit area of the drying surface is uniform (Fortes & Okos, 1980; Macey, 1942; Moore, 1961). The evaporation rate is close to that of an open dish of liquid, as indicated by the data for the drying of alumina gel (Dwivedi, 1986), shown in Fig. 6. The rate may differ slightly, depending on the texture of the surface. For example, as sand beds dry, the water conforms to the shapes of the particles, so the wet area is larger than the planar one pertaining to the surface of the body, and the rate of evaporation is correspondingly higher (Ceaglske & Hougen, 1937). The distribution of a spreading liquid is illustrated schematically in Fig.6. The chemical potential, µ, of the liquid in the adsorbed film is equal to the one under the concave meniscus, otherwise liquid would flow from one to the other to balance the potential. The chemical potential µ is lower than bulk liquid because of disjoining and capillary forces,

where p0 is the vapour pressure of bulk liquid, Rg is the ideal gas constant, T is the temperature and Δµ is the increment of the chemical potential. The rate of evaporation, VE,

where k is a coefficient that depends on the design of the drying chamber, draft rate, etc. It appears reasonable to conclude that the surface of the body must be covered with a film of liquid (as in Fig. 6a), because the rate would decrease as the body shrinks if evaporation

Fig. 6. Distribution of liquid at the surface of a drying porous body, when liquid is (a) spreading (contact angle θ=0°) or (b) wetting, but not spreading (90°> θ >0°). The chemical

potential of the liquid in the adsorbed film is equal to that under the meniscus.

� ������� �⁄ ��� (6)

�� � ����� ����� (7)

therefore the vapour pressure (pv) decreases according to:

occurrs only from the menisci, Fig. 6b.

�� ��

is proportional to the difference between pv and the ambient vapour pressure, pA:

## **3.1 Sol-gel synthesis of organic – inorganic hybrid materials**

Hybrid organic-inorganic biomaterials were prepared by means of a sol-gel process from an analytical reagent grade of metal alkoxides M(OR)x, in an ethanol, organic polymer like poli-ε-caprolactone (PCL Mw = 65,000), water and solvent (CHCl3) mixture. Water, diluted with ethanol was added to the solution under a vigorous stirring. A flow-chart of hybrids (MO2 + PCL x wt%) can show the synthesis by the sol-gel method. MO2/PCL, all mixed with drugs (y wt%), were also prepared by using an analytical reagent grade as a precursor material.

In this study SiO2/PCL (PCL 0, 6, 12, 50 wt%) materials were used as support matrices for controlled drug release. Silica gel, originally developed for engineering applications, is also currently being studied as a polymer for the entrapment and sustained release of drugs (Teoli et al., 2006). In the present study the sol-gel method was applied to encapsulate Ketoprofen (5, 10, 15 wt%) as a model drug. The drug loaded amorphous bioactive materials were studied in terms of their drug release kinetics

The hybrid inorganic-organic materials (PCL 0, 6, 12, 50 wt%) were prepared by means of sol-gel process from an analytical reagent grade of tetraethyl orthosilicate (TEOS) in an ethanol, poly-ε-caprolactone (PCL ), water, and chloroform (CHCl3) mixture. Water, diluted with ethanol was added to the solution under vigorous stirring. Fig. 7 shows the flow chart of hybrid (SiO2 + %PCL + %Ketoprofen) synthesis by the sol-gel method. As it is shown in the same Fig. 7, SiO2/PCL (PCL 0, 6, 12, 50 wt%) all mixed with ketoprofen (5, 10, 15 %) were prepared by using an analytical reagent grade as precursor material.

After the addition of each reactant the solution was stirred and the resulting sols were uniform and homogeneous. The gelification time was controlled by varying the concentration of PCL, as shown in Tab. 4. After gelification the gels were air dried at 50°C for 24h to remove the residual solvent; as this treatment does not modify the stability of ketoprofen, glassy pieces were obtained (Fig. 8). Discs with a diameter of 13 mm and a thickness of 2 mm were obtained by pressing a fine (<125 μm) gel powder into a cylindrical holder.

Fig. 7. Flow chart of SiO2/PCL gel synthesis.


Table 4. Variation in the gelification time, controlled by changing the concentration of PCL.

Fig. 8. SiO2/PCL gel after drying.

Chromatographic experiments were carried out on a Shimadzu HPLC system, equipped with a Class-VP 5.0 software, an UV spectrophotometric detector SPD-10AVvp and two pumps LC-10ADvp, with low-pressure gradient systems. Samples of solutions were injected by a syringe via a Rheodyne loop injector; the loop volume was 20 μl, the analytical column was a Phenomenex C18 (150 × 4.60 mm; 5 μ); the flow rate of the mobile phase A (water) was set at 0.8 ml/min and that of the mobile phase B (methanol) was set at 0.2 ml/min. The total runtime was 10 minutes. HPLC grade methanol was obtained by Sigma-Aldrich. HPLC grade water was prepared using a Millipore (0.22 μm) system. A standard solution of ketoprofen 3 mM in a simulated body fluid (SBF) was prepared and the samples were taken at the end of the release from the materials.

The nature of SiO2 gel, poly-ε-caprolactone (PCL) and PCL/SiO2 hybrid materials were ascertained by X-ray diffraction (XRD) analysis using a Philips diffractometer. The presence of hydrogen bonds between organic-inorganic components of the hybrid materials was ascertained by FTIR analysis. Fourier transform infrared (FTIR) transmittance spectra were recorded in the 400-4000 cm-1 region using a Prestige 21 Shimatdzu system, equipped with a DTGS KBr (Deuterated Tryglycine Sulphate with potassium bromide windows) detector, with resolution of 2 cm-1 (45 scans). KBr pelletized disks containing 2 mg of sample and 200 mg KBr were made. The FTIR spectra were elaborated by IR solution software. The microstructure of the synthesized gels was studied by a scanning electron microscopy (SEM) Cambridge model S-240 on samples previously coated with a thin Au film and by a Digital Instruments Multimode atomic force microscopy (AFM) in contact mode in air.
