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Method for evaluating drug release from liposomes in sink conditions

by Paula Saarinen-Savolainen, Tomi Järvinen, Hannu Taipale, Arto Urtti
International Journal of Pharmaceutics ()
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An in vitro method was developed for the evaluation of the drug release from disperse systems, such as liposomes, under sink conditions. Determination of in vitro release of lipophilic drugs from liposomes requires a dissolution medium that maintains sink conditions without damaging the lipid membrane and a method to separate the released drug from the liposomal drug. We propose a new in vitro technique for the evaluation of drug release from liposomes using a hydrophilic β-cyclodextrin derivative in the dissolution medium to maintain sink conditions. A liposomal drug dispersion was placed in a magnetically stirred dialysis bag (Mw cut-off 300 000) containing cyclodextrins to provide sink conditions. The released drug was sampled from the outside of the bag. Release of hydrocortisone and budesonide from different multilamellar liposomes 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-α- phosphatidylcholine (DSPC) liposomes than in liquid-phase, L-α- phosphatidylcholine (EPC) liposomes. Leakage of encapsulated calcein from the liposomes was not affected by cyclodextrins suggesting that they do not disturb the structure of the lipid bilayers. This method is capable of distinguishing different true release rates of drugs from colloidal carriers and it is easy to perform.

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