From the above equation, it can be seen that as the amount of coarse lactose and fine lactose are increased, they may lead to high fine particle fraction. This might be due to easy detachment of the drug from the coarse lactose due to its high adhesion onto the low adhesion sites of the coarse lactose. Thus lung deposition majorly depends on the optimum ratio of coarse and file lactose as well as mixing time or lactose with drug.
The contour plots and the overlay plot with the design space has been shown in Fig. 3.
Scanning electron microscopy
The SEM studies of preblend of coarse and fine lactose were done to see whether the fine lactose occupies the high adhesion sites of coarse lactose or not. The SEM
images as shown in Fig. 4 show that the fine lactose has covered majority of the high adhesion sites of the coarse lactose.
In vitro deposition studies of optimized batch using eight stage nonviable cascade impactor
188.8.131.52 Mass balance and in vitro
The mass balance study of the optimized batch was done prior to in vitro deposition studies. The mass balance was 98.63% which was within the acceptable range of 85-115%, showing no drug loss in the system. Cascade impactor is the best tool for the in vitro evaluation of the inhalation products due to several merits. It helps in the determination of mass median aerodynamic diameter which plays a significant role in determining the
Figure 3. Response surface plots of design batches and overlay curve
NUJPS – 2019 | Vol. 6 | Issue 1 65
Table 4 Mass balance and fine particle fraction of the optimized batch
||Mass Balance (%)
||Fine particle fraction (%)
||Mass median aerodynamic diameter (µm)
||98.63 ± 3.41
||8.99 ± 3.71
||3.40 ± 0.02
Figure 4. SEM image of dry powder inhaler blend (optimized batch)
Figure 5. Amount of drug deposited on various stages of cascade impactor and image of S1 plate
66 INHALED FLUTICASONE PROPIONATE DRY POWDER FOR THE EFFECTIVE MANAGEMENT…
deposition of the drug in several parts of the lungs. It also helps to determine the
bronchitis, asthma and pulmonary emphysema. Am Rev Respir Dis
fine particle fraction of the drug.
consists of eight stages with a cut-off diameter ranging between 0.7 and 10 µm. The mass median aerodynamic diameter as well as fine particle fraction of the optimized batch has been shown in Table 4 and the amount of drug deposited at various stages has been shown in Fig.5.
The fluticasone propionate dry powder formulation was prepared and evaluated systematically. The optimized formulation showed mass median aerodynamic diameter between 1-5 µm and fine particle fraction of 8.99% using Breezhaler® device. This represents the effectiveness of the dry powder inhalation formulation in the efficient delivery of fluticasone propionate into the lungs which can be useful for the successful treatment of severe disease such as asthma.
The authors would thank Institute of Pharmacy, Nirma University for providing all the facilities for carrying out our research work. We also thank Meggle Germany and DFE Pharma for providing us inhalable lactose grades.
- Scadding JG. Definitions and clinical categories of asthma. In: Clark TJH, Godfrey S, eds. Asthma. 2nd ed. London: Chapman and Hall, 1983:1-
- American Thoracic Society. Definition and classifications of chronic
- Enright PL, McClelland RL, Newman AB, Gottlieb DJ, Lebowitz Underdiagnosis and undertreatment of asthma in the elderly. Cardiovascular Health Study Research Group. Chest. 1999;116(3):603–613.
- Zureik M, Orehek J. Diagnosis and severity of asthma in the elderly: results of a large survey in 1,485 asthmatics recruited by lung Respiration. 2002;69(3):223–228.
- Telko MJ, and Hickey, AJ: Dry powder inhaler formulation. Respir care. 2005; 50: 1209-27.
- Frijlink H, and Boer AH De: Dry powder inhalers for pulmonary drug delivery. Expert opin drug 2004;1: 67-86.
- Mehta Dry powder inhalers: A focus on advancements in novel drug delivery systems. J Drug Deliv. 2016; 2016: 8290963. (doi: 10.1155/2016.8290963)
- P.NEWMAN* AND W.W. BUSSEw. Evolution of dry powder inhaler design, formulation, and performance. Vol. 96 (2002) 293-304.
- G. AYRES*, A. B. MILLAR i” AND A. P. SYKES. Clinical efficacy and safety of fluticasone propionate 1 mg twice daily administered via a HFA 134a pressurized metered dose inhaler to patients with severe asthma. Respir Med. 2009; 98(2): 503-15.
NUJPS – 2019 | Vol. 6 | Issue 1 67
Booth H, Richmond I, Ward C, Gardiner PV, Harkawat R, Walters Effect of high dose inhaled fluticasone propionate on airway inflammation in asthma. Am J Res pir Crit Ca re Med 1995; 152: 45–52.
- Barnes NC, Marone G, Di Maria GU, Visser S, Utama I, Payne SL. A comparison of fluticasone propionate,
1 mg daily, with beclomethasone dipropionate, 2 mg daily, in the treatment of severe asthma. Eur Respir J 1993; 6: 877-884.
- Olivieri D, Chetta A, Del Donno M, et a l. Effect of short-term tre atment with low-dose inhaled fluticasone propionate on airway inflammation and remodeling in mild asthma: a placebo-controlle d Am J Res p ir Crit Ca re Me d 1997; 155: 1864–1871.
- Misaka S, Sato H, Yamauchi Y, Onoue S, and Yamada S: Novel dry powder formulation of ovalbumin for development of COPD-like animal model: Physicochemical characterization and biomarker profiling in rats. Eur J Pharm Sci. 2009; 37: 469-76.
- S. Pharmacopoeia: USP 29 Section 1174. Powder flow. Available from: www.pharmacopeia.cn/v29240/usp29 nf24s0_c1174.html. (Last accessed on 5th May, 2017).
- European Pharmacopoeia 1 Preparations for inhalation. Available from: http://library.njucm.edu.cn/ yaodian/ep/EP501E/02_methods_of_a
nalysis/2.9. pharmaceutical_technica l_procedures/2.9.18. Preparations for inhalation aerodynamic assessment of fine particles/2.9.18.pdf (Last accessed on 5th May, 2017).
- Tougas T, Christopher D, Mitchell JP, Strickland H, Wyka B, Oort MV, and Lyapustina S: Improved quality control metrics for cascade impaction measurements of Orally Inhaled Drug Products (OIPs). AAPS 2009; 10: 1276-85.
- Rawal , Parmar R., Tyagi R.K., Butani S. Rifampicin loaded chitosan nanoparticle dry powder presents an improved therapeutic approach for alveolar tuberculosis. 2017; 154: 321- 330.
- Kinnunen H, Hebbink G, Peters H, Shur J, and Price R: An investigation into the effect of fine lactose particles on the fluidization behaviour and aerosolization performance of carrier- based dry powder inhaler AAPS PharmSciTech. 2014; 15: 898–909.
- L. Chow, H.Y. Tong, P. Chattopadhyay, B. Shekunov, Particle engineering for pulmonary drug delivery, Pharm. Res. 24 (3) (2007) 411–437.
- El-Gendy, M.M. Bailey, C. Berkland, Particle engineering technologies for pulmonary drug delivery, Controlled pulmonary drug delivery, Springer, 2011, pp. 283–312.