Co-spraying of carriers (mannitol-lactose) as a method to improve aerosolization performance of salbutamol sulfate dry powder inhaler

Drug Delivery and Translational Research - Tập 10 - Trang 1418-1427 - 2020
Mickey Socrates Ferdynand1, Ali Nokhodchi1,2
1Pharmaceutics Research Laboratory, School of Life Sciences, University of Sussex, Brighton, UK
2Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

Tóm tắt

Although in dry powder inhaler (DPI) formulations a single carrier is used, a single carrier is not able to provide an excellent aerosolization performance when it is used in DPI formulations. Thereby, the aim of this study was to engineer a suitable ternary mixture of mannitol-lactose-leucine to be used in a DPI formulation with enhanced aerosolization performance. To this end, binary mixtures of mannitol:lactose containing a constant amount of leucine (5% w/w of carriers) were spray-dried as a single solution. Spray-dried samples were blended with salbutamol sulfate to determine the efficiency of their aerosolization performance. Interestingly, note that lactose was in its amorphous state stabilized by the presence of mannitol in the samples. Spray-dried mannitol without lactose showed a combination of the α- and β-polymorphic forms which was the case in all other ratios of mannitol:lactose. It was shown that the highest fine particle fraction (FPF) was 62.42 ± 4.21% which was obtained for the distinct binary mixtures (1:3 mannitol:lactose) compared to a single carrier. This study opens a new window to investigate further the implementation of binary mixtures of sugar carriers containing leucine in DPI formulations to overcome poor aerosolization performance the mentioned DPI formulations.

Tài liệu tham khảo

Bai TR. Beta 2 adrenergic receptors in asthma: a current perspective. Lung. 1992;170:125–41. Bateman JR, Pavia D, Sheahan NF, Agnew JE, Clarke SW. Impaired tracheobronchial clearance in patients with mild stage asthma. Thorax. 1983;38:463–7. Adcock IM, Gilbey T, Gelder CM, et al. Glucocorticoid receptor localisation in normal and asthmatic lungs. American J Respiratory Critical Care Med. 1996;154:771–82. Wilson SM, Shen P, Rider CF, Traves SL, Proud D, Newton R, et al. Selective prostacyclin receptor agonism augments glucocorticoid-induced gene expression in human bronchial epithelial cells. J Immun. 2009;183:6788–99. Adi S, Adi H, Tang P, Traini D, Chan HK, Young PM. Micro-particle corrugation, adhesion and inhalation aerosol efficiency. Eur J Pharm Sci. 2008;35:12–8. Hassan MS, Lau R. Inhalation performance of pollen-shape carriers in dry powder formulation with different drug mixing rations: comparison with lactose carrier. Int J Pharm. 2010;386:6–14. Molina C, Kaialy W, Chen Q, Commandeur D, Nokhodchi A. Agglomerated novel spray-dried lactose-leucine tailored as a carrier to enhance the aerosolization performance of salbutamol sulfate from DPI formulations. Drug Del Trans Res. 2018;8:1769–80. Agnoletti M, Bohr A, Thanki K, Wan F, Zeng X, Boetker JP, et al. Inhalable siRNA-loaded nano-embedded microparticles engineered using microfluidics and spray drying. Eur J Pharm Biopharm. 2017;120:9–21. Haj-Ahmad R, Rasekh M, Nazari K, Li Y, Fu Y, Li B, et al. EHDA spraying: a multi-material nano-engineering route. Curr Pharm Des. 2015;21:3239–47. Raula J, Thielmann F, Kansikas J, et al. Investigations on the humidity-induced transformations of salbutamol sulfate particles coated with L-leucine. Pharm Res. 2008;25:2250–61. Aquino RP, Prota L, Auriemma G, et al. Dry powder inhalers of gentamicin and leucine: formulation parameters, aerosol performance and in vitro toxicity on CuFi1 cells. Int J Pharm. 2012;426:100–7. Seville PC, Learoyd TP, Li HY, et al. Amino acidmodified spray-dried powders with enhanced aerosolisation properties for pulmonary drug delivery. Powder Technol. 2007;178:40–50. Feng AL, Boraey MA, Gwin MA, Finlay PR, Kuehl PJ, Vehring R. Mechanistic models facilitate efficient development of leucine containing microparticles for pulmonary drug delivery. Int J Pharm. 2011;409:156–63. Boraey MA, Hoe S, Sharif H, et al. Improvement of the dispersibility of spray-dried budesonide powders using leucine in an ethanol–water cosolvent system. Powder Technol. 2013;236:171–8. Shur J, Nevell TG, Ewen RJ, Price R, Smith A, Barbu E, et al. Cospray-dried unfractionated heparin with leucine as a dry powder inhaler mucolytic for cystic fibrosis therapy. J Pharm Sci. 2008;97:4857–68. Chang Y-X, Yang J-J, Pan R-L, et al. Anti-hygroscopic effect of leucine on spray-dried herbal extract powders. Powder Technol. 2014;266:388–95. Otake H, Okuda T, Hira D. Inhalable spray-freeze-dried powder with L-leucine that delivers particles independent of inspiratory flow pattern and inhalation device. Pharm Res. 2016;33:922–31. Li L, Sun S, Parumasivam T. L-Leucine as an excipient against moisture on in vitro aerosolization performances of highly hygroscopic spray-dried powders. Eur J Pharm Biopharm. 2016;102:132–41. Chang YX, Yang JJ, Pan L. Anti-hygroscopic effect of leucine on spray-dried herbal extract powders. Powder Technol. 2014;266:388–95. Kaialy W, Hussain T, Alhalaweh A, Nokhodchi A. Towards a more desirable dry powder inhaler formulation: large spray-dried mannitol microspheres outperform small microspheres. Pharm Res. 2014;31:60–76. Kaialy W, Martin GP, Ticehurst MD, et al. The enhanced aerosol performance of salbutamol from dry powders containing engineered mannitol as excipient. Int J Pharm. 2010;392:178–88. Molina C, Kaialy W, Nokhodchi A. The crucial role of leucine concentration on spray-dried mannitol-leucine as a single carrier to enhance the aerosolization performance of Albuterol sulfate. J Drug Del Sci Technol. 2019;49:97–106. Kaialy W, Larhrib H, Martin GP, Nokhodchi A. The effect of engineered mannitol-lactose mixture on dry powder inhaler performance. Phram Res. 2012;29:2139–56. Yang JJ, Liu CY, Quan LH, Liao YH. Preparation and in vitro aerosol performance of spray-dried Shuang-Huang-Lian corrugated particles in carrier-based dry powder inhalers. AAPS PharmSciTech. 2012;13:816–25. US Pharmacopeia. {601} Aerosols, nasal sprays, metered-dose inhalers, and dry powder inhaler (general chapter). United States Pharmacopeia. 35th-NF ed. FDA, See Tittle 21 Code of Federal Regulations, 1998. Le VNP, Hoang Thi TH, Robins E, Flament MP. Dry powder inhalers: study of the parameters influencing adhesion and dispersion of fluticasone propionate. AAPS Pharm Sci Tech. 2012;13:477–84. Kaialy W, Martin GP, Ticehurst MD, Royall P, Mohammad MA, Murphy J, et al. Characterisation and deposition studies of recrystallised lactose from binary mixtures of ethanol/butanol for improved drug delivery from dry powder inhalers. AAPS J. 2011;13:30–43. Poozesh S, Bilgili E. Scale-up of pharmaceutical spray drying using scale-up rules: a review. Int J Pharm. 2019;562:271–92. Jones MD, Harris H, Hooton JC, Shur J, King GS, Mathoulin CA, et al. An investigation into the relationship between carrier-based dry powder inhalation performance and formulation cohesive-adhesive force balances. Eur J Pharm Biopharm. 2008;69:496–507. Kaialy W, Alhalaweh A, Velaga S, Nokhodchi A. Influence of lactose carrier particle size on the aerosol performance of budesonide from a dry powder inhaler. Powder Technol. 2012;227:74–85. Owen MK, Ensor DS. Airborne particle sizes and sources found in indoor air. Atmos Environ Part A Gen Top. 1992;26:2149–62. Shur J, Price R, Lewis D, Young P, Woollam G, Singh D, et al. From single excipients to dual excipient platforms in dry powder inhaler products. Int J Pharm. 2016;514:374–83.