In this chapter, a range of characterization techniques for proliposomes and the resultant liposomes were elucidated, and their importance was discussed. For proliposomes, characterization techniques include X-ray diffraction to investigate powder crystallinity, particle morphology study using scanning electron microscopy (SEM) and angle of repose (AOR) to study proliposome flowability. These characteristics of proliposome powders are a result of the formulation design and can influence their aerosol performance, and the characteristics of the subsequently generated liposomes. Liposome characteristics are usually investigated in terms of particle size using laser diffraction (for micro-size vesicles) or dynamic light scattering (for nano-liposomes), zeta potential using electrophoretic mobility, and vesicle morphology and lamellarity using transmission electron microscopy (TEM). Proliposome formulations are delivered in inhalable aerosols either as proliposome powder, proliposome solution, or as liposome dispersion (following hydration of proliposomes). A limited number of studies were conducted on the delivery of proliposomes using pressurized metered dose inhalers (pMDIs), which was achieved by dissolving the lipid blend in chlorofluorocarbon (CFC) propellants in which the drug is dissolved or dispersed (depending on its propellant-solubility). Precise proliposome doses can be generated from pMDIs, resulting in immediate evaporation of the propellant and presumed hydration of lipids-drug blend into liposomes in situ by utilizing the aqueous environment of the lung. The replacement of the ozone-depleting CFC propellants with the non-ozone depleting hydrofluoroalkanes (HFAs) has limited the research of liposomes/proliposome delivery via pMDIs, because HFAs are poor solubilizes of phospholipids. Many research studies were conducted on the delivery of particulate-based proliposomes using dry powder inhalers (DPIs), mostly using spray drying to manufacture the proliposomes. Superiorly high proliposome aerosol performance could be achieved and assessed in vitro, depending on formulation composition. Medical nebulizers have shown a great capability of delivering liposomes generated from particulate-based or ethanol-based proliposomes. Proliposomes can utilize the shearing environment within nebulizer reservoir and convert in situ into inhalable liposomes. Air-jet and vibrating-mesh nebulizers have shown the ability to generate highly performing aerosols from this proliposome system, while the ultrasonic device delivered only 6% of the phospholipid content, suggesting its unsuitability for delivering this proliposome system. Many other studies of nebulizing liposomes generated from proliposome powders or dispersed tablets have been elucidated and evaluated in this chapter.

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Formulation Approaches for Proliposomes in Pulmonary Drug Delivery

  • Abdelbary Elhissi,
  • Dana Elkhalifa,
  • Iftikhar Khan,
  • Waqar Ahmed

摘要

In this chapter, a range of characterization techniques for proliposomes and the resultant liposomes were elucidated, and their importance was discussed. For proliposomes, characterization techniques include X-ray diffraction to investigate powder crystallinity, particle morphology study using scanning electron microscopy (SEM) and angle of repose (AOR) to study proliposome flowability. These characteristics of proliposome powders are a result of the formulation design and can influence their aerosol performance, and the characteristics of the subsequently generated liposomes. Liposome characteristics are usually investigated in terms of particle size using laser diffraction (for micro-size vesicles) or dynamic light scattering (for nano-liposomes), zeta potential using electrophoretic mobility, and vesicle morphology and lamellarity using transmission electron microscopy (TEM). Proliposome formulations are delivered in inhalable aerosols either as proliposome powder, proliposome solution, or as liposome dispersion (following hydration of proliposomes). A limited number of studies were conducted on the delivery of proliposomes using pressurized metered dose inhalers (pMDIs), which was achieved by dissolving the lipid blend in chlorofluorocarbon (CFC) propellants in which the drug is dissolved or dispersed (depending on its propellant-solubility). Precise proliposome doses can be generated from pMDIs, resulting in immediate evaporation of the propellant and presumed hydration of lipids-drug blend into liposomes in situ by utilizing the aqueous environment of the lung. The replacement of the ozone-depleting CFC propellants with the non-ozone depleting hydrofluoroalkanes (HFAs) has limited the research of liposomes/proliposome delivery via pMDIs, because HFAs are poor solubilizes of phospholipids. Many research studies were conducted on the delivery of particulate-based proliposomes using dry powder inhalers (DPIs), mostly using spray drying to manufacture the proliposomes. Superiorly high proliposome aerosol performance could be achieved and assessed in vitro, depending on formulation composition. Medical nebulizers have shown a great capability of delivering liposomes generated from particulate-based or ethanol-based proliposomes. Proliposomes can utilize the shearing environment within nebulizer reservoir and convert in situ into inhalable liposomes. Air-jet and vibrating-mesh nebulizers have shown the ability to generate highly performing aerosols from this proliposome system, while the ultrasonic device delivered only 6% of the phospholipid content, suggesting its unsuitability for delivering this proliposome system. Many other studies of nebulizing liposomes generated from proliposome powders or dispersed tablets have been elucidated and evaluated in this chapter.