Impact of dispersion media and carrier type on spray-dried proliposome powder formulations loaded with beclomethasone dipropionate for their pulmonary drug delivery via a next generation impactor

Abstract

Drug delivery via aerosolization for localized and systemic effect is a non-invasive approach to achieving pulmonary targeting. The aim of this study was to prepare spray-dried proliposome (SDP) powder formulations to produce carrier particles for superior aerosolization performance, assessed via a next generation impactor (NGI) in combination with a dry powder inhaler. SDP powder formulations (F1-F10) were prepared using a spray dryer, employing five different types of lactose carriers (Lactose monohydrate (LMH), lactose microfine (LMF), lactose 003, lactose 220 and lactose 300) and two different dispersion media. The first dispersion medium was comprised of water and ethanol (50:50% v/v ratio), and the second dispersion medium comprised wholly of ethanol (100%). In the first dispersion medium, the lipid phase (consisting of Soya phosphatidylcholine (SPC as phospholipid) and Beclomethasone dipropionate (BDP; model drug) were dissolved in ethanol and the lactose carrier in water, followed by spray drying. Whereas in second dispersion medium, the lipid phase and lactose carrier were dispersed in ethanol only, post spray drying. SDP powder formulations (F1-F5) possessed significantly smaller particles (2.89 ± 1.24-4.48 ± 1.20 μm), when compared to SDP F6-F10 formulations (10.63 ± 3.71-19.27 ± 4.98 μm), irrespective of lactose carrier type via SEM (scanning electron microscopy). Crystallinity of the F6-F10 and amorphicity of F1-F15 formulations were confirmed by XRD (X-ray diffraction). Differences in size and crystallinity were further reflected in production yield, where significantly higher production yield was obtained for F1-F5 (74.87 ± 4.28-87.32 ± 2.42%) then F6-F10 formulations (40.08 ± 5.714-54.98 ± 5.82%), irrespective of carrier type. Negligible differences were noted in terms of entrapment efficiency, when comparing F1-F5 SDP formulations (94.67 ± 8.41-96.35 ± 7.93) to F6-F10 formulations (78.16 ± 9.35-82.95 ± 9.62). Moreover, formulations F1-F5 demonstrated significantly higher fine particle fraction (FPF), fine particle dose (FPD) and respirable fraction (RF) (on average of 30.35%, 890.12 μg and 85.90%) when compared to counterpart SDP powder formulations (F6-F10). This study has demonstrated that when a combination of water and ethanol was employed as dispersion medium (formulations F1-F5), superior formulation properties for pulmonary drug delivery were observed, irrespective of carrier type employed.

Fig 1. Scanning electron microscope images of coarse lactose carriers (Lactose monohydrate (LMH), lactose microfine (LMF), lactose 003, lactose 220 and lactose 300) (a-e), and spray-dried proliposome (SDP) powder formulations (F1-F5) using a dispersion medium of ethanol and water (50:50% v/v), and SDP powder formulations (F6-F10) when ethanol 100% was used as a dispersion medium.

These images are typical of three such different experiments.

Fig 2. Production yield of spray-dried proliposome powder formulations when water and ethanol (50:50% v/v) was used as a dispersion medium (F1 –F5), and when ethanol alone (100%) was used as dispersion medium (F6 –F10).

Data are mean ± STD, n = 3; *p<0.05 for F6 –F10 compared to F1 –F5.

Fig 3. Particle size of spray-dried proliposome (SDP) powder formulations, where water and ethanol (50:50% v/v) was employed as a dispersion medium (F1 –F5), and SDP powder formulations (F6 –F10) when ethanol (100%) was used as dispersion medium.

Data are mean ± STD, n = 3; *p<0.05 for F1 –F5 compared to F6 –F10.

Fig 4. X-ray diffraction spectrum for BDP (alone), and five types of lactose carriers (Lactose monohydrate (LMH), lactose microfine (LMF), lactose 003, lactose 220 and lactose 300), followed by their incorporation and formulations of spray-dried proliposome (SDP) powder formulations (F1-F5) when water and ethanol (50:50% v/v) was used as a dispersion medium, and SDP powder formulations (F6-F10) when ethanol alone was used 100% as a dispersion medium.

This data is typical of three such different experiments.

Fig 5. Moisture content of coarse lactose carriers (Lactose monohydrate (LMH), lactose microfine (LMF), lactose 003, lactose 220 and lactose 300), spray-dried proliposome (SDP) powders (F1-F5) where water and ethanol (50:50% v/v) was used as a dispersion medium, and SDP powders (F6-F10) where ethanol (100%) was only used as a dispersion medium.

Data are mean ± STD, n = 3; *p<0.05 for F1 –F5 compared to F6 –F10 and LMH, LMF, L003, L220, L300; p>0.05 for F6 –F10 compared to LMH, LMF, L003, L220, L300.