A novel "slurry method" was described for the preparation of proliposome powders using soya phosphatidylcholine (SPC) with cholesterol (1:1) and for incorporation of beclometasone dipropionate (BDP) at 2mole% of the total lipid phase. Proliposomes made with a range of lipid to sucrose carrier ratios were studied in terms of surface morphology using scanning electron microscopy (SEM) and thermal properties using differential scanning calorimetry (DSC). Following hydration of proliposomes, the resultant vesicles were compared to liposomes made using the traditional proliposome method, in terms of vesicle size and drug entrapment efficiency. SEM showed that sucrose was uniformly coated with lipid regardless of lipid to carrier ratio. Liposomes generated using the slurry proliposome method tended to have smaller median size than those generated with the conventional proliposome method, being in the range of 4.72-5.20μm and 5.89-7.72μm respectively. Following centrifugation of liposomes using deuterium oxide (D2O) as dispersion medium, vesicles entrapping BDP were separated as a floating creamy layer, whilst the free drug was sedimented as crystals. Drug entrapment was dependent on formulation composition and preparation method. When 1:15 w/w lipid to carrier was used, liposomes generated using the slurry method had an entrapment efficiency of 47.05% compared to 18.67% for those generated using the conventional proliposome method. By contrast, liposomes made by the thin-film hydration method had an entrapment efficiency of 25.66%. DSC studies using 50mole% BDP demonstrated that the drug was amorphous in the proliposome formulation and tended to crystallize on hydration, resulting in low drug entrapment. In conclusion, a novel approach to the preparation of proliposomes using a slurry method has been introduced, offering higher entrapment for BDP than liposomes made using the conventional proliposome method and those prepared by thin-film hydration technique.

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Formulation effects on the entrapment of beclometasone dipropionate (BDP) in liposomes generated by hydration of proliposomes were studied, using the high-density dispersion medium deuterium oxide in comparison to deionized water (DW). Proliposomes incorporating BDP (2 mol% of the lipid phase consisting of soya phosphatidylcholine (SPC) and cholesterol; 1:1) were manufactured, using lactose monohydrate (LMH), sorbitol or D-mannitol as carbohydrate carriers (1:5 w/w lipid to carrier). Following hydration of proliposomes, separation of BDP-entrapped liposomes from the unentrapped (free) BDP at an optimized centrifugation duration of 90 min and a centrifugation force of 15,500g were identified. The dispersion medium was found to have a major influence on separation of BDP-entrapped liposomes from the unentrapped drug. Entrapment efficiency values were higher than 95% as estimated when DW was used. By contrast, the entrapment efficiency was 19.69 ± 5.88, 28.78 ± 4.69 and 34.84 ± 3.62% upon using DO as a dispersion medium (for LMH-, sorbitol- and D-mannitol-based proliposomes, respectively). The similarity in size of liposomes and BDP crystals was found to be responsible for co-sedimentation of liposomes and free BDP crystals upon centrifugation in DW, giving rise to the falsely high entrapment values estimated. This was remedied by the use of DO as confirmed by light microscopy, nuclear magnetic resonance (HNMR), X-ray diffraction (XRD) and entrapment studies. This study showed that carrier type has a significant influence on the entrapment of BDP in liposomes generated from proliposomes, and using DO is essential for accurate determination of steroid entrapment in the vesicles.