Influence of a charged phospholipid on the release pattern of timolol maleate from cubic liquid crystalline phases

Abstract

The release of timolol maleate, a drug for treatment of glaucoma, from cubic liquid crystals consisting of charged and uncharged lipids was investigated in vitro. It was shown that the release of drug was dependent on the ionic strength of the receptor medium and the relative amount of a charged phospholipid in the cubic phase. In the absence of charged lipids, the release of timolol was complete, irrespective of the medium used, i.e. distilled water or saline solution. In the presence of a negatively charged phospholipid, diacylphosphatidylglycerol, the release of drug from the cubic phase was incomplete when distilled water was the receptor medium. The residual drug was dependent on the amount of charged lipid in the cubic phase. In saline solution, on the other hand, all of the drug was released. The results are interpreted as an effect of electrostatic attraction between the positively charged drug with the negatively charged bilayer surface, which is screened in the presence of saline. The possible influence of the cubic geometry is discussed as well. This work shows that lipids offer many possibilities in the formulation of sustained drug release systems.

This paper is dedicated to Prof. Kåre Larsson at the time of his retirement from academic duties