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fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Omer, Huner Kamal
Languages: English
Types: Doctoral thesis
Subjects:
This study describes developments and in vitro characterisation of lipid microparticles prepared using spray-drying for drug delivery to the lung via dry powder inhalers. Bioadhesive formulations such as prochitosome or chitosome powders have been introduced to overcome the drawbacks of liposome instability and potentially provide significant increase in the residence time of drug in the lung. \ud Mannitol or lactose monohydrate (LMH) aqueous solutions were spray dried at inlet temperatures of 90, 130, 170 or 210ºC. Soy phosphatidylcholine and cholestrol (1:1 mole ratio) were used in all formulations. Cholesterol was added to increase vesicle membrane rigidity. Proliposomes containing salbutamol sulphate (SS) were prepared by incorporating various lipid:carrier (mannitol or LMH; 1:2, 1:4, 1:6, 1:8 and 1:10 w/w). Prochitosomes including SS or beclomethason dipropionate (BDP) were prepared by adding various chitosan glutamate:lipid ratios of 1:10, 2:10, 3:10 and 5:10 w/w. Chitosomes, including various cryoprotectants (mannitol, LMH, trehalose or sucrose), were prepared by including chitosan glutamate to liposomes generated from ethanol-based proliposomes in the ratio of 3:10 w/w chitosan to lipid. The spray-drying parameters for generation of dry powders were optimised by using an inlet temperature of 120ºC, outlet temperature of 73 ± 3°C, aspirator rate of 100%, suspension feed rate of 11%, and spray flow rate of 600 L/h using B-290 Buchi mini spray-dryer.\ud The production yields were 48.1±2.84%, 69.73±2.05%, 61.33±2.51% and 58.0±3.0% for mannitol and 50.66±3.51%, 68.0±2.0%, 73.66±1.52%, 59.0±2.64% for LMH at 90, 130, 170 or 210ºC, respectively. The size of the particles were smaller than 5 µm for both carriers at of 90 and 130 ºC, whilst larger than 5 µm at inlet temperatures of 170 and 210 ºC. Particles had smooth, spherical and smaller size at 90 and 130 ºC than inlet temperatures of 170 and 210 ºC. Mannitol kept its crystalline properties after spray-drying, whilst LMH changed to amorphous at all drying temperatures.\ud Mannitol-based proliposome particles were uniform, small and spherically shaped. In contrast, LMH-based proliposome particles were irregular and large. Entrapment efficiency of SS was higher for LMH-based proliposomes, however, fine particle fraction (FPF) was higher for proliposomes containing mannitol. Higher FPF was obtained for proliposome containing lipid to mannitol ratio of 1:6 (FF= 52.6%). Vesicles size decreased with increasing carrier ratio and the zeta potential was slightly negative for all formulations studied.\ud Prochitosomes were small, porous and spherically shaped particles. Higher FPF was achieved for prochitosome powders containing chitosan to lipid ratio of 3:10 and 5:10 for both SS (FPF = 58.12±2.86% and 70.25±2.61% respectively) and BDP (FPF = 61.89±9.04% and 61.56±3.13% respectively). Zeta potential and the fraction of mucin adsorbed on the vesicles increased upon increasing chitosan concentration. Vesicle size decreased with increasing chitosan concentration. Entrapment efficiency (EE) of the formulations containing BDP was higher than that for SS. Moreover, the drug EE was higher using chitosomes compared to liposomes.\ud LMH and trehalose-based liposome or chitosome particles were spherical with less tendency of agglomeration compared to mannitol and sucrose-based particles. Powders containing LMH, trehalose or sucrose were amorphous, whilst mannitol-based powder was crystalline. The FPF values were 14.39±1.81%, 32.29±0.15, 48.99±2.22% and 50.79±3.19% for mannitol, sucrose, LMH and trehalose-based liposome formulations, respectively. However, FPF% values were higher for chitosomes, being 23.48±3.38%, 33.89±0.66%, 54.88±1.85% and 55.9±2.74% for mannitol, sucrose, LMH and trehalose-based chitosomes, respectively. The EE of SS was increased upon coating liposome surface with chitosan regardless of cryoprotectant type. \ud In conclusion, the findings of this study have demonstrated the potential of lipid microparticles in pulmonary drug delivery and that prochitosomes or chitosomes may offer great potential for enhancing drug resident time in the lung.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

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