Abstract
PurposeThe aim of this study was to develop and compare proliposome powder and proliposome tablet formulations for drug delivery from a Pari-LC Sprint nebulizer.MethodsProliposome powders were prepared by the slurry method and sorbitol or mannitol carbohydrate carrier were used in a 1:10 and 1:15 w/w lipid phase to carrier ratio. Beclometasone dipropionate (BDP; 2 mol%) was incorporated in the lipid phase. Proliposome powders were compressed into tablets, and liposomes were generated from proliposome powders or tablets within the nebulizer reservoir for subsequent aerosolization.ResultsComparatively, shorter sputtering times were reported for the tablet formulations (≈ < 2.7±0.45 min), indicating uniform aerosolization. Post-nebulization, liposomes size was larger in the nebulizer reservoir in the range of 7.79±0.48 µm–9.73±1.53 µm for both powder and tablet formulations as compared to freshly prepared liposomes (5.38±0.73 µm–5.85±0.86 µm), suggesting liposome aggregation/fusion in the nebulizer’s reservoir. All formulations exhibited more than 80% mass output regardless of formulation type, but greater BDP proportions (circa 50%) were delivered to the Two-stage Impinger when tablet formulations were used. Moreover, the nebulized droplet median size and size distribution were lower for all tablet formulations in comparison to the powder formulations. Proliposome tablet and powdered formulations demonstrated the ability to generate vesicles that sustained the release of BDP.ConclusionOverall, this study showed that proliposome tablets could be disintegrated within a Pari-LC Sprint nebulizer to generate inhalable aerosol, with high drug output and hence can be manufactured on large scale to overcome the storage problems associated with powder formulations.
Highlights
Aerosol formulations have been employed for pulmonary drug delivery to achieve localized treatment for respiratory and other immune-mediated diseases (Waldrep. 1998; Godet et al 2017)
This research aimed to investigate and establish differences between proliposome powder and tablet formulations prepared in different ratios using Beclometasone dipropionate (BDP) as a model drug
Proliposome powder or tablet formulations hydrated in nebulizer reservoir (Pari-LC Sprint nebulizer), exhibited similar nebulization time, shorter sputtering time was found for all tablet formulations demonstrating more progressive and consistent aerosolization during nebulization
Summary
Aerosol formulations have been employed for pulmonary drug delivery to achieve localized treatment for respiratory and other immune-mediated diseases (Waldrep. 1998; Godet et al 2017). The pulmonary system offers a large surface area (82–100 m 2), facilitating fast drug absorption to the systemic circulation (Khan et al 2013, 2016). Deep lung deposition, associated with better treatment outcomes, is challenging. Pulmonary formulations and devices are areas of continuous research (Khan et al 2013). Medical nebulizers are devices used to generate inhalable aerosol, offering deep lung deposition, mostly for immediate drug release. Liposomes have been investigated for around five decades as drug carriers in pulmonary inhalation. This is due to their ability to entrap hydrophilic and hydrophobic drugs
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