Erosion and controlled release properties of semisolid vesicular phospholipid dispersions

Abstract

Phosphatidylcholine, when dispersed in aqueous medium in high concentrations (300 mg/g and above) by high pressure homogenisation, forms semisolid pastes of vesicular morphology. The multivesicular matrix can accommodate hydrophilic compounds in the aqueous compartments. The disintegration and release of hydrophilic marker of these dispersions were studied in vitro by using a flow-through cell. Slow release of the marker over periods of hours up to days took place via two different mechanisms: (1) erosion of the matrix with release of marker-filled liposomes and marker which had been trapped in between the liposomes and (2) diffusion of marker through the membranes. Whereas for lipid concentrations up to 300 mg/g almost spontaneous disintegration occurred, more concentrated pastes (350–400 mg/g) showed zero-order erosion kinetics for 4–6 h. Erosion was rate limiting for overall release. For 450 and 500 mg/g lipid dispersions, the release of free marker followed square root of time kinetics for 13 or 21 h, respectively, which is typical for matrix-controlled diffusion. Underlying the diffusion was a slow zero-order erosion of the matrix. The results are important for the future development of vesicular phospholipid gels as sustained release therapeutic system, e.g. as implantable depot.