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Proliposome Powders for the Generation of Liposomes: the Influence of Carbohydrate Carrier and Separation Conditions on Crystallinity and Entrapment of a Model Antiasthma Steroid

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Abstract

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 D2O 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 D2O as confirmed by light microscopy, nuclear magnetic resonance (1HNMR), 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 D2O is essential for accurate determination of steroid entrapment in the vesicles.

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Acknowledgements

We thank Lipoid, Switzerland, for supplying us with soya phosphatidylcholine (SPC, Lipoid S-100).

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Authors and Affiliations

  1. School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, L3 3AF, Liverpool, UK

    Iftikhar Khan

  2. Institute of Nanotechnology and Bioengineering, University of Central Lancashire, Preston, PR1 2HE, UK

    Iftikhar Khan, Sakib Yousaf, Sneha Subramanian & Mohamed Albed Alhnan

  3. School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE, UK

    Iftikhar Khan, Sakib Yousaf, Sneha Subramanian & Mohamed Albed Alhnan

  4. School of Mathematics and Physics, College of Science, University of Lincoln, Lincoln, LN6 7TS, UK

    Waqar Ahmed

  5. Pharmaceutical Sciences Section, College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar

    Abdelbary Elhissi

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  1. Iftikhar Khan
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Correspondence to Abdelbary Elhissi.

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Khan, I., Yousaf, S., Subramanian, S. et al. Proliposome Powders for the Generation of Liposomes: the Influence of Carbohydrate Carrier and Separation Conditions on Crystallinity and Entrapment of a Model Antiasthma Steroid. AAPS PharmSciTech 19, 262–274 (2018). https://doi.org/10.1208/s12249-017-0793-2

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