P. Saarinensavolainen et al., METHOD FOR EVALUATING DRUG-RELEASE FROM LIPOSOMES IN SINK CONDITIONS, International journal of pharmaceutics, 159(1), 1997, pp. 27-33
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.