METHOD FOR EVALUATING DRUG-RELEASE FROM LIPOSOMES IN SINK CONDITIONS

An in vitro method was developed for the evaluation of the drug releas e from disperse systems, such as liposomes, under sink conditions. Det ermination of in vitro release of lipophilic drugs from liposomes requ ires a dissolution medium that maintains sink conditions without damag ing the lipid membrane and a method to separate the released drug from the liposomal drug. We propose a new in vitro technique for the evalu ation of drug release from liposomes using a hydrophilic P-cyclodextri n derivative in the dissolution medium to maintain sink conditions. A liposomal drug dispersion was placed in a magnetically stirred dialysi s bag (Mw cut-off 300000) containing cyclodextrins to provide sink con ditions. The released drug was sampled from the outside of the bag. Re lease of hydrocortisone and budesonide from different multilamellar li posomes was measured. True release rate was evaluated from the release data of liposomal and free drug from the dialysis bags, respectively. Release of steroids from the liposomes was relatively fast, but they were retained longer in gel-phase, distearoyl-L-a phosphatidylcholine (DSPC) liposomes than in liquid-phase, L-cr-phosphatidylcholine (EPC) liposomes. Leakage of encapsulated calcein from the liposomes was not affected by cyclodextrins suggesting that they do not disturb the stru cture of the lipid bilayers. This method is capable of distinguishing different true release rates of drugs from colloidal carriers and it i s easy to perform. (C) 1997 Elsevier Science B.V.