WETTABILITY STUDIES ON DRUGS AND DRUG DELIVERY VESICLES

The surface properties of selected drugs and liposomes (drug delivery vesicles) were characterized by two independent techniques: contact angle and sedimentation volume methods. Firstly, advancing contact angles THETA-A, of different liquids were measured on compressed powders of drugs (tablets) and on layers of liposomes. The contact angles were determined by means of the sessile drop method, and in some cases by the axisymmetric drop shape analysis - contact diameter technique (ADSA-CD). The surface tensions, gamma-SV, were then calculated from the contact angles measured on the different surfaces. Secondly, another method, the sedimentation volume, V(sed), technique was applied to estimate directly the solid/vapour surface tensions of drug powders and those of the liposomes originally suspended in binary liquid mixtures. The experiments were performed with six different drugs used both in powdered form (V(sed)) and as powder compacts (contact angle). Multilamellar (MLV) liposomes were prepared from phospholipid (PL) and cholesterol (Chol) in different molar ratios. Both empty liposomes (without drug) and drug loaded vesicles were investigated as dispersions for the sedimentation experiments and as deposited liposomal layers for the contact angle measurements. The surface tensions obtained from V(sed) and calculated from THETA-A for the drugs showed an agreement. The order of the hydrophobicity of the drugs can be established from these results. It was also found that the surface tensions of the empty liposomes with different PL/Chol ratios depend on their composition: the hydrophilic character of liposomes decreases with the increasing cholesterol content. Sedimentation results indicated that the encapsulated drug might affect the surface properties of liposomes. The effect of drug depends on the PL/Chol molar ratio as well as on the properties and the concentration of the encapsulated drug. It was found that the change in surface properties of liposomal layers due to drug encapsulation cannot be detected by the traditional (sessile drop) contact angle measuring method. However, the ADSA-CD technique provided higher sensitivity. The surface tensions obtained for the deposited layers of drug loaded vesicles by this technique were similar to those obtained from the V(sed) studies performed with liposome dispersions.