ENCAPSULATION AND EFFLUX OF LACTONE AND HYDROXY ACID FORMS OF SIMVASTATIN IN REVERSE-PHASE EVAPORATION VESICLES

Simvastatin (SV) is the lactone prodrug of SVA, a hydroxymethylglutaryl-CoA reductase inhibitor, which in its active form of a hydroxy acid (SVA) lowers plasma cholesterol through inhibiting its endogenous synthesis. The present paper describes an attempt to encapsulate both drugs in reverse-phase evaporation (REV) vesicles. The experimental results can be summarized as follows: (i) both drugs (SV and SVA) are encapsulated efficiently into DPPC liposomes with high yield; (ii) in all preparations tested, the more hydrophilic SVA is encapsulated to a considerably greater extent than SV, reaching approx. 60% in the case of DPPC liposomes; (iii) the presence of cholesterol in the vesicle wall markeldy reduces this capacity; (iv) it is possible to control the release of drug from the liposomes by modifying the lipid composition of the vesicles. The procedure of encapsulation into liposomes in principle should permit the direct administration of SVA, thereby reducing the toxicity associated with high doses of SV.