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-CoAre ductasei nhibitor, which in its activef orm of a hydroxya cid (SVA) lowersp lasmac holesterolt hrough inhibiting its endogenouss ynthesisT. he presentp aper describesa n attempt to encapsulateb oth drugsi n reverse-phasee vaporation( REV) vesicles.T he experimentalr esultsc an be summarizeda s follows: (i) both drugs( SV and SVA) are encapsulatede fficiently into DPPC liposomesw ith high yield; (ii) in all preparationst ested,t he more hydrophilic SVA is encapsulatedto a considerablyg reater extent than SV, reaching approx.6 0Voi n the caseo f 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 liposomesb y modifuingt he lipid compositiono f the vesiclesT. he procedureo f encapsulatioinn to liposomesin principle should permit the direct administrationo f SVA, thereby reducingt he toxicity associatedw ith high doseso f SV.