MONTELUKAST SPRAY DRIED MICROPARTICLES: PREPARATION, EXCIPIENTS SELECTION AND IN VITRO PULMONARY DEPOSITION

  • Roxane Abdelgawad Moussa Department of Pharmaceutics and Industrial Pharmacy, Teaching Assistant, Faculty of Pharmacy, Ain Shams University, Egypt
  • Rihab Osman Ain Shams University
  • Gehane A.s. Awad Ain Shams University
  • Nahed Mortada Ain Shams University

Abstract

Objective: This study focused on the preparation of montelukast sodium (MTK) fast release pulmonary targeted microparticles using the spray drying technique.

Methods: The effect of addition of different excipients namely: mannitol, leucine and ovalbumin on the physico-chemical characteristics of MTK spray dried powders were investigated. Powder flow properties, drug association efficiency as well as microparticle size and mass median aerodynamic diameter were determined. The prepared microparticles were characterized using FT-IR and TGA. The powder crystallographic and thermal properties were studied using DSC and X-ray powder diffraction. A twin stage impinger was used to evaluate in vitro pulmonary deposition from which the inhalation indices were derived.

Results: The tested excipients showed no adverse chemical interactions with the drug based on FT-IR. The best inhalation indices were obtained with powders spray dried with leucine followed by leucine/mannitol mixtures with MMAD of 1.73±0.08 and 1.36±0.16 and fine particle fraction of 60.55±1.63 and 52.31±3.52, respectively. The dried powders showed good physico-chemical stability for up to 6 mo storage.

Conclusion: The developed MTK spray dried particles may offer a good platform for the targeted pulmonary delivery of MTK overcoming the major biological barriers.

Keywords: Montelukast, Spray drying, Microparticles, Pulmonary delivery, Mannitol, Albumin, Leucine

Downloads

Download data is not yet available.

References

1. Daniher D, Zhu J. Dry powder platform for pulmonary drug delivery. Particuology 2008;6:225-38.
2. Beck-Broichsitter M, Merkel O, Kissel T. Controlled pulmonary drug and gene delivery using polymeric nano-carriers. J Controlled Release 2012;161:214-24.
3. Al-Hamdani F. Comparative clinical evaluation of ketotifen and montelukast sodium in asthmatic Iraqi patients. Saudi Pharm J 2010;18:245-9.
4. Blume C, Davies D. In vitro and ex vivo models of human asthma. Eur J Pharm Biopharm 2013;84:394-400.
5. Rubinstein I, Kumar B, Schriever C. Long-term montelukast therapy in moderate to severe COPD—a preliminary observation. Respir Med 2004;98:134-8.
6. Lipworth B. Leukotriene-receptor antagonists. Lancet 1999;353:57-62.
7. Osman R, Kan P, Awad G, Mortada N, El-shamy A, Alpar O. Spray dried inhalable ciprofloxacin powder with improved aerosolisation and antimicrobial activity. Int J Pharm 2013;449:44-58.
8. Yang W, Peters J, Williams R. Inhaled nanoparticles-a current review. Int J Pharm 2008;356:239-47.
9. Mobley C, Hochhaus G. Methods used to assess pulmonary deposition and absorption of drugs. Drug Discovery Today 2001;6:367-75.
10. Sung J, Pulliam B, Edwards D. Nanoparticles for drug delivery to the lungs. Trends Biotechnol Sci 2007;25:563-70.
11. Evora C, Soriano I, Rogers R, Shakesheff K, Hanes J, Langer R. Relating the phagocytosis of microparticles by alveolar macrophages to surface chemistry: the effect of 1,2-dipalmitoylphosphatidylcholine. J Controlled Release 1998;51:143-52.
12. Weingart J, Vabbilisetty P, Sun X. Membrane mimetic surface functionalization of nanoparticles: Methods and applications. Adv Colloid Interface Sci 2013;197–198:68-84.
13. Roa W, Azarmi S, Al-hallak M, Finlay W, Magliocco A, Lobenberg R. Inhalable nanoparticles, a non-invasive approach to treat lung cancer in a mouse model. J Controlled Release 2011;150:49-55.
14. El-Sherbiny M, El-Baz M, Yacoub M. Inhaled nano-and microparticles for drug delivery. Global Cardiol Sci Practice J 2015;2:1:14.
15. Daviskas E, Anderson S, Eberl S, Young I. Beneficial effect of inhaled mannitol and cough in asthmatics with mucociliary dysfunction. Respir Med 2010;104:1645-53.
16. Yamasaki K, Kwok P, Fukushige K, Prud'homme R, Chan H. Enhanced dissolution of inhalable cyclosporine nano-matrix particles with mannitol as matrix former. Int J Pharm 2011;420:34-42.
17. Wu L, Miao X, Shan Z, Huang Y, Li L, Pan X, et al. Studies on the spray dried lactose as carrier for dry powder inhalation. Asian J Pharm Sci 2014;9:336-41.
18. Zeng X, Martin G, Marriott C. Preparation and in vitro evaluation of tetrandrine-entrapped albumin microspheres as an inhaled drug delivery system. Eur J Pharm Sci 1995;3:87-93.
19. Chan H. Dry powder aerosol drug delivery-opportunities for colloid and surface scientists. Colloids Surf A 2006;284–285:50-5.
20. Puttewar T, Kshirsagar M, Chandewar A, Chikhale R. Formulation and evaluation of orodispersible tablet of taste masked doxylamine succinate using ion exchange resin. J King Saud Univ Sci 2010;22:229-40.
21. Traina K, Cloots R, Bontempi S, Lumay G, Vacewalle N, Boschini F. Flow abilities of powders and granular materials evidenced from dynamical tap density measurement. Powder Technol 2013;235:842-52.
22. Awasthi R, Kulkarni G. Development and characterization of amoxicillin loaded floating microballoons for the treatment of Helicobacter pylori induced gastric ulcer. Asian J Pharm Sci 2013;8:174-80.
23. Oskouie A, Noll K, Wang H. Minimizing the effect of density in determination of particle aerodynamic diameter using a time of flight instrument. J Aerosol Sci 2003;34:501-6.
24. Geuns E, Toren J, Barends D, Bult A. Decrease of the stage-2 deposition in the twin impinger during storage of beclomethasone dipropionate dry powder inhalers in controlled and uncontrolled humidities. Eur J Pharm Biopharm 1997;44:187-94.
25. Young P, Price R. The influence of humidity on the aerosolisation of micronised and SEDS produced salbutamol sulphate. Eur J Pharm Sci 2004;22:235-40.
26. Le V, Hoang Thi T, Robins E, Flament M. Dry powder inhalers: study of the parameters influencing adhesion and dispersion of fluticasone propionate. AAPS Pharm Sci Tech 2012;13:477-84.
27. Nakate T, Yoshida H, Ohike A, Tokunaga Y, Ibuki R, Kawashima Y. Formulation development of inhalation powders for FK888 using the E-haler® to improve the inhalation performance at a high dose, and its absorption in healthy volunteers. Eur J Pharm Biopharm 2005;59:25-33.
28. Yan C, Wu Q, Zhang Z, Yuan L, Liu X, Zhou L. Preparation of curcumin-loaded liposomes and evaluation of their skin permeation and pharmacodynamics. Molecules 2012;17:5972-87.
29. Zhao Q, Wang T, Wang J, Zheng L, Jiang T, Cheng G, et al. Template-directed hydrothermal synthesis of hydroxyapatite as a drug delivery system for the poorly water-soluble drug carvedilol. Appl Surf Sci 2011;257:10126-33.
30. Moreira G, Maia M, Souza A, Brito E, Medeiros M, Azeredo H. Physical properties of spray dried acerola pomace extract as affected by temperature and drying aids. LWT-Food Sci Technol 2009;42:641-5.
31. Ruohui L, Wenjie L, Meng W, Cordelia S, Xiao C. Formation of crystalline amino acid particles via spray drying. Chemeca 2013: Challenging Tomorrow conference; 2013. p. 575-80.
32. Sinsuebpol C, Chatchawalsaisin J, Kulvanich P. Preparation and in vivo absorption evaluation of spray dried powders containing salmon calcitonin loaded chitosan nanoparticles for pulmonary delivery. Drug Des Dev Ther 2013;7:861-73.
33. Geldart D, Abdullah E, Hassanpour A, Nwoke L, Wouters I. Characterization of powder flowability using measurement of angle of repose. China Particuol 2006;4:104-7.
34. Shah R, Tawakkul M, Khan M. Comparative evaluation of flow for pharmaceutical powders and granules. AAPS Pharm Sci Tech 2008;9:250-8.
35. Lebrun P, Krier F, Mantanus J, Grohganz H, Yang M, Rozet E, et al. Design space approach in the optimization of the spray-drying process. Eur J Pharm Biopharm 2012;80:226-34.
36. Fernández Tena A, Casan Clarà P. Deposition of inhaled particles in the lungs. Archivos de Bronconeumología 2012;48:240-6.
37. Hastedt J, Cabot K, Gong D, Hester D. Storage stable powder compositions of interleukin-4 receptor; 2007.
38. Patil-Gadhe A, Pokharkar V. Montelukast-loaded nanostructured lipid carriers: part I oral bioavailability improvement. Eur J Pharm Biopharm 2014;88:160-8.
39. Sahoo N, Kakran M, Abbas A, Judeh Z, Li L. Preparation, characterization and dissolution behavior of artemisinin microparticles. Adv Powder Technol 2011;22:458-63.
40. Maas S, Schaldach G, Littringer E, Mescher A, Griesser U, Braun D, et al. The impact of spray drying outlet temperature on the particle morphology of mannitol. Powder Technol 2011;213:27-35.
41. Feng A, Gwin M, Finlay P, Bennett M, Boraey M, Kuehl P, et al. Rational design of microparticels for respiratory drug delivery using L-Leucine. Int J Pharm 2011;409:156-63.
42. Alnabari M, Sery Y, Adin I, Arad O, Kaspi J. Stable amorphous forms of montelukast sodium; 2009.
43. Bilgic M. Stable pharmaceutical combinations; 2010.
44. Mahajan H, Gundare S. Preparation, characterization and pulmonary pharmacokinetics of xyloglucan microspheres as dry powder inhalation. Carbohydr Polym 2014;102:529-36.
45. Hulse W, Forbes R, Bonner M, Getrost M. The characterization and comparison of spray-dried mannitol samples. Drug Dev Ind Pharm 2009;35:712-8.
46. Adhikari S, Kar T. Bulk single crystal growth and characterization of l-leucine–A nonlinear optical material. Mater Chem Phys 2012;133:1055-9.
47. Priyanka K, Abdul Hasan S. Preparation and evaluation of montelukast sodium loaded solid lipid nanoparticles. J. Young Pharm 2012;4:129-37.
Statistics
505 Views | 1846 Downloads
How to Cite
Moussa, R. A., R. Osman, G. A. Awad, and N. Mortada. “MONTELUKAST SPRAY DRIED MICROPARTICLES: PREPARATION, EXCIPIENTS SELECTION AND IN VITRO PULMONARY DEPOSITION”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 7, no. 11, Oct. 2015, pp. 233-40, https://innovareacademics.in/journals/index.php/ijpps/article/view/8668.
Section
Original Article(s)