Preparation and Evaluation of Acyclovir Liposomes by Two Techniques: A Comparative Study

The aim of this study was to prepare liposomes of acyclovir (ACY) by thin layer evaporation (TLE) and reverse phase evaporation (REV) methods. Twenty-seven batches of liposomes from each method were prepared using technique of three variables at three levels (3³) factorial design. Drug/Lipid (molar ratio), hydration volume and hydration time were considered three independent variables in TLE method while that of Drug/Lipid (molar ratio), organic phase volume and aqueous phase volume in REV method. Liposomes, obtained by TLE method (TLEs) and REV method (REVs) were evaluated for geometric mean diameter, and percent drug entrapment (PDE). REVs of 3.5(2.3) µm with 77.2% and of 3.4(2.2) µm with 71.1% drug entrapment was obtained with Drug/PC/CHOL (in molar ratio) of 1:4:0.5 and 1:2:0.5 respectively while TLEs of 4.3(1.7) µm with 79.5% drug entrapment was obtained with Drug/PC/CHOL (in molar ratio) of 1:20:10. In vitro studies were conducted to compare drug diffusion pattern across the human cadaver skin (HCS) of promising batches of TLEs and REVs. A significantly low (p<0.05) flux [0.628(0.046) µg/cm²/h] obtained by TLEs when compared with the flux [0.785(0.050) µg/cm²/h] obtained by REVs across HCS. The flux values of ACY TLEs and REVs revealed the lamellarity. Low flux in TLEs than REVs across HCS indicated the formation of multilamellar vesicles (MLVs) in TLE method while oligolamellar vesicles (OLVs) with few lamellae surrounding the large aqueous core in REV method. Multilamellarity of the TLEs makes the liposomes to supply drug in more sustained way in the layer of HCS as indicated by high amount of drug deposition (350.7 µg) in the HCS after 72 h of application when compared with drug deposition in the HCS (321.0 µg) for the same period by REVs.

Thus, the finding of the study establishes the role of REV method producing OLVs of ACY with high PDE using 5-10 fold less amount of high costing phosphatidylcholine when compared to MLVs prepared by TLE method with insignificant change in PDE but significant change in flux, which affects the release of drug at the target site.