The Effect of Solvent Treatment on the Performance of Various Carriers in Dry Powder Inhalations Containing Salbutamol Sulphate

Document Type : Original Article


1 1Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

2 2Medway School of Pharmacy, University of Kent, Chatham, ME4 4TB, Kent, UK

3 1Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran 2Medway School of Pharmacy, University of Kent, Chatham, ME4 4TB, Kent, UK



It has been suggested that the efficiency of dry poder inhaler (DPI) is generally low. Therefore, the aim of the present research work was to use the solvent treatment of the carrier in DPIformulations to see the possibility of inducing desirable characteristics.
Materials and Methods:
Lactose sieve fractions of 63-90 μm were submerged in ethanol or 80% v/v ethanol, methanol or propanol. Lactose crystals were then blended with either 1% w/w or 4% w/w salbutamol sulphate using a Turbula mixer. Drug detachment was studied using a multistage liquid. Laser particle size analyzer, DSC, and pycnometer were used to characterize the treated lactose and mannitol samples. SEM was used to study surface morphologies. In case of mannitol as a carrier only ethanol was used as a solvent.
SEM images displayed less rugosities and increased surface smoothness after submersion. Although the tomahawk like shape remained fairly constant in most lactose samples, the solvent treatment changed the shape of mannitol particles which was proved by SEM results. Deposition results showed that the type of solvent had an influence on fine particle fraction. In addition, the payload had also a big impact on fine particle fraction values. Generally, treated samples showed better performance compared to untreated samples. Solid state analysis by DSC showed that no major changes occurred in the treated samples compared to untreated samples.
The solvent treated method can be used as an approach to improve the performance of carriers such as lactose and mannitol in dry powder inhaler.


1. Prime D, Atkins P, Slater A, Bumby B. Review of drug powder inhalers. Adv drug Rev 1997; 22:51-58.
2. Timsina MP, Martin GP, Marriott C, Ganderton D, Yianneskis M. Drug delivery to the respiratory tract using dry powder inhalers. Int J Pharm 1994; 101:1-13.
3. Flament MP, Leterme P, Gayot A. The influence of carrier roughness on adhesion, content uniformity and in vitro deposition of terbutaline sulphate from drug powder inhalers. Int J Pharm 2004; 275:201-209.
4. Zeng X, Martin G, Mariott C, Pritchard J. The influence of carrier morphologies on drug delivery by dry powder inhalers. Int J Pharm 2000; 200:93-106.
5. Larhib H, Martin G, Marriott C, Prime D. The influence of carrier and drug morphologies on drug delivery from dry powder formulations. Int J Pharm 2003; 257:283-296.
6. Dickhoff B, Boer A, Lambregts D, Frijlink H. The effect of carrier surface treatment or drug particle detachment crystalline carriers in adverse mixtures for inhalation. Int J Pharm 2006; 327:17-25.
7. Kaialy W, Martin GP, Larhrib H, Ticehurst MD, Kolosionek E, Nokhodchi A. The influence of physical properties and morphology of crystallised lactose on delivery of salbutamol sulphate from dry powder inhalers. Colloid Surf B 2012; 89:29-39.
8. Kaialy W, Ticehurst MD, Murphy J, Nokhodchi A. Improved aerosolization performance of salbutamol sulphate formulated with lactose crystallised from binary mixtures of ethanol-acetone. J Pharm Sci 2011; 100:2665-2684.
9. Kaialy W, Larhrib H, Ticehurst MD, Nokhodchi A. Influence of batch cooling crystallization on mannitol physical properties and drug dispersion from dry powder inhalers. Cryst Growth Des 2012; 12:3006-3017.
10. Kaialy W, Momin MN, Ticehurst MD, Murphy J, Nokhodchi A. Engineered mannitol as an alternative carrier to enhance deep lung penetration of salbutamol sulphate from dry powder inhaler. Colloid Surf B 2010; 79:345-56.
Dry Powder Inhalation Performance Siahai Shadbad et al
Iran J Basic Med Sci, Vol. 16, No. 7, Jul 2013
11. Kaialy W, Martin GP, Ticehurst MD, Momin MN, Nokhodchi A. The enhanced aerosol performance of salbutamol from dry powders containing engineered mannitol as excipient. Int J Pharm 2010; 392:178-88.
12. Carr RL. Classifying flow properties of solids. Chem Eng 1965; 72:169-172.
13. Carr RL. Evaluating flow properties of solids. Chem Eng 1965; 72:163-168.
14. Machado JJB, Coutinho JA, Macedo EA. Solid-liquid equilbrium of α-lactose in ethanol/water. Fluid Phase Equ 2000; 173:121-134.
15. Dickhoff BHJ, de Boer AH, Lambregts D, Frijlink HW. The effect of carrier and bulk properties on particle detachment from crystalline lactose carrier particles during inhalation, as function of carrier payload and mixing time. Eur J Pharm Biopharm 2003; 56:291-302.
16. Zeng X, Martin G, Mariott C, Pritchard J. The use of lactose recrystallised from carbopol gels as a carrier from aerosolised Salbutamol Sulphate., Eur J Pharm Biopharm 2001; 51:55-62.
17. De Boer AH, Hagedoorn P, Gjaltema D, Goede J, Kussendrager K, Frijlink HW. The effect of lactose carrier surface properties on the deagglomeration of adhesive mixtures in a basic classifier. Int J Pharm 2003; 260:201-216.
18. Steckel H, Muller BW. In vitro evaluation of dry powder inhalers II: influence of carrier particle size and concentration on in vitro deposition. Int J Pharm 1997; 154:31-37.
19. Iida K, Hayakawa Y, Okamoto H, Danjo K, Leuenberger H. Preparation of dry powder inhalation by surface treatment of lactose carrier particles. Chem Pharm Bull 2003; 51:1-85.
20. Colombo P, Catellani PL, Massimo G, Santi P, Bettini R, Cocconi D, et al. Surface smoothing of lactose particles for dry powder inhalers. In: Dalby RN, Byron PR, Farr SJ, Peart J. editos. Respiratory Drug Delivery VII. Inc, Raleigh, England: Serentec Press; 2000.p. 629-631.
21. Heng PW, Chan LW, Lim LT. Quantification of the surface morphologies of lactose carriers and their effect on the in vitro deposition of salbutamol sulphate. Chem. Pharm Bull 2000; 48:393-398.
22. Steckel H, Markefka P, TeWierik H, Kammelar R. Effect of milling and sieving on functionality of dry powder inhalation products. Int J Pharm 2006; 309:51-59.
23. Podczeck,F. The influence of particle size distribution and surface roughness of carrier particles on the in vitro properties of dry powder inhalations. Aer Sci Technol 1999; 31:301–321.
24. Young PM, Edge S, Daniela T, Jones M, Price R, El-Sabawi D, et al. The influence of dose on the performance of dry powder inhalation systems. Int J Pharm 2005; 296:26-33.
25. Tee SK, Marriott C, Zeng XM, Martin GP. The use of different sugars as fine and coarse carriers for aerosolised salbutamol sulphate. Int J Pharm 2003; 208:111-123.