Skip to main content

Advertisement

SpringerLink
Log in

Development of Budesonide Microparticles Using Spray-Drying Technology for Pulmonary Administration: Design, Characterization, In Vitro Evaluation, and In Vivo Efficacy Study

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The purpose of this research was to generate, characterize, and investigate the in vivo efficacy of budesonide (BUD) microparticles prepared by spray-drying technology with a potential application as carriers for pulmonary administration with sustained-release profile and improved respirable fraction. Microspheres and porous particles of chitosan (drug/chitosan, 1:2) were prepared by spray drying using optimized process parameters and were characterized for different physicochemical parameters. Mass median aerodynamic diameter and geometric standard deviation for conventional, microspheres, and porous particles formulations were 2.75, 4.60, and 4.30 µm and 2.56, 1.75, and 2.54, respectively. Pharmacokinetic study was performed in rats by intratracheal administration of either placebo or developed dry powder inhalation (DPI) formulation. Pharmacokinetic parameters were calculated (Ka, Ke, T max, C max, AUC, and Vd) and these results indicated that developed formulations extended half life compared to conventional formulation with onefold to fourfold improved local and systemic bioavailability. Estimates of relative bioavailability suggested that developed formulations have excellent lung deposition characteristics with extended T 1/2 from 9.4 to 14 h compared to conventional formulation. Anti-inflammatory activity of BUD and developed formulations was compared and found to be similar. Cytotoxicity was determined in A549 alveolar epithelial cell line and found to be not toxic. In vivo pulmonary deposition of developed conventional formulation was studied using gamma scintigraphy and results indicated potential in vitro–in vivo correlation in performance of conventional BUD DPI formulation. From the DPI formulation prepared with porous particles, the concentration of BUD increased fourfold in the lungs, indicating pulmonary targeting potential of developed formulations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

ACFs:

attenuation correction factors

ACI:

Anderson cascade impactor

AUC:

area under the curve

BALF:

bronchoalveolar lavage fluid

BUD:

budesonide

CI:

Carr's index

COPD:

chronic obstructive pulmonary disease

DCM:

dichloromethane

DPI:

dry powder inhaler

DSC:

differential scanning calorimetry

ED:

emitted dose

EI:

effective index

FPF:

fine particle fraction

GSD:

geometric standard deviation

hPBMCs:

human peripheral blood mononuclear cells assay

HPMC:

hydroxypropyl methyl cellulose

ICSs:

inhaled corticosteroids

IL-6:

interleukin-6

Ka:

absorption rate constant

Ke:

elimination rate constant

MEK:

methyl ethyl ketone

LPS:

lipopolysaccharide

MMAD:

mass median aerodynamic diameter

OECD:

Organization for Economic Co-operation and Development

SEM:

scanning electron microscope

TNF-α:

tumor necrosis factor-alpha

tR:

retention time

TSI:

twin stage impinger

Vd:

apparent volume of distribution

XRPD:

X-ray powder diffraction

References

  1. Szefler SJ. Pharmacodynamics and pharmacokinetics of budesonide: a new nebulized corticosteroid. J Allergy Clin Immunol. 1999;104:S175–83.

    Article  CAS  Google Scholar 

  2. Basyigit I, Yildiz F, Ozkara SK, Yildirim E, Boyaci H, Ilgazli A. Addition of inhaled corticosteroid on combined bronchodilator therapy in patients with COPD. Pulm Pharmacol Ther. 2005;20:1–5.

    Google Scholar 

  3. Cazzola M. Single inhaler budesonide/formoterol in exacerbations of chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2006;19:79–89.

    Article  PubMed  CAS  Google Scholar 

  4. Thorsson L, Borga O, Edsbacker S. Systemic availability of budesonide after nasal administration of three different formulations: pressurized aerosol, aqueous pump spray, and powder. Br J Clin Pharmacol. 1999;47:619–24.

    Article  PubMed  CAS  Google Scholar 

  5. Learoyd TP, Burrows JL, French E, Seville PC. Chitosan-based spray-dried respirable powders for sustained delivery of terbutaline sulfate. Eur J Pharm Biopharm. 2008;68:224–34.

    Article  PubMed  CAS  Google Scholar 

  6. Fu J, Fiegel J, Krauland E, Hanesa J. New polymeric carriers for controlled drug delivery following inhalation or injection. Biomaterials. 2002;23:4425–33.

    Article  PubMed  CAS  Google Scholar 

  7. Koushik K, Kompella UB. Particle & device engineering for inhalation drug delivery. Drug Deliv Technol. 2004;4:40–50.

    CAS  Google Scholar 

  8. Ribeiro AJ, Silva C, Ferreira D, Veiga F. Chitosan-reinforced alginate microspheres obtained through the emulsification/internal gelation technique. Eur J Pharm Biopharm. 2005;25:31–40.

    CAS  Google Scholar 

  9. Sanna V, Kirschvink N, Gustin P, Gavini E, Roland I, Delattre L, et al. Preparation and in vivo toxicity study of solid lipid microparticles as carrier for pulmonary administration. AAPS PharmSciTech. 2003;5:1–7.

    Google Scholar 

  10. Irngartinger M, Camuglia V, Damm M, Goede J, Frijlink HW. Pulmonary delivery of therapeutic peptides via dry powder inhalation: effects of micronisation and manufacturing. Eur J Pharm Biopharm. 2004;58:7–14.

    Article  PubMed  CAS  Google Scholar 

  11. Jashnani RN, Byron PR, Dalby RN. Testing of dry powder aerosol formulations in different environmental conditions. Int J Pharm. 1995;113:123–30.

    Article  CAS  Google Scholar 

  12. Sommerville ML, Hickey AJ. Aerosol generation by metered-dose inhalers containing dimethyl ether/propane inverse microemulsions. AAPS PharmSciTech. 2003;4:1–7.

    Article  Google Scholar 

  13. Leach CL, Davidson PJ, Boudreau RJ. Improved airway targeting with the CFC-free HFA–beclomethasone metered-dose inhaler compared with CFC–beclomethasone. Eur Respir J. 1998;12:1346–53.

    Article  PubMed  CAS  Google Scholar 

  14. Chougule MB, Padhi BK, Jinturkar KA, Misra A. Development of dry powder inhalers. Recent Patents on Drug Delivery and Formulation. 2007;1:11–21.

    Article  PubMed  CAS  Google Scholar 

  15. Johnson KA. Preparation of peptide and protein powders for inhalation. Adv Drug Deliv Rev. 1997;26:3–15.

    Article  PubMed  CAS  Google Scholar 

  16. Yu Z, Rogers TL, Hu J, Johnston KP, Williams RO. Preparation and characterization of microparticles containing peptide produced by a novel process: spray freezing into liquid. Eur J Pharm Biopharm. 2002;54:221–8.

    Article  PubMed  CAS  Google Scholar 

  17. Zeng XM, Martin GP, Tee SK, Marriott C. The role of fine particle lactose on the dispersion and deaggregation of salbutamol sulphate in an air stream in vitro. Int J Pharm. 1998;176:99–110.

    Article  CAS  Google Scholar 

  18. Larhrib H, Martin GP, Marriott C, Prime D. The influence of carrier and drug morphology on drug delivery from dry powder formulations. Int J Pharm. 2003;257:283–96.

    Article  PubMed  CAS  Google Scholar 

  19. Smith IJ, Billings MP. The inhalers of the future? A review of dry powder devices on the market today. Pulm Pharmacol Ther. 2003;16:79–95.

    Article  PubMed  CAS  Google Scholar 

  20. Schnurch AB. Chitosan and its derivatives: potential excipients for peroral peptide delivery systems. Int J Pharm. 2000;194:1–13.

    Article  Google Scholar 

  21. Cook RO, Pannu RK, Kellaway IW. Novel sustained release microspheres for pulmonary drug delivery. J Control Release. 2005;104:79–90.

    Article  PubMed  CAS  Google Scholar 

  22. Spoelstra FM, Postma DS, Hovenga H, Noordhoek JA, Kauffman HF. Budesonide and formoterol inhibit ICAM-1 and VCAM-1 expression of human lung fibroblasts. Eur Respir J. 2000;15:68–74.

    Article  PubMed  CAS  Google Scholar 

  23. Uings I, Puxeddu I, Temkin V, Smith SJ, Fattah D, Ray KP, et al. Effects of dexamethasone on TNF-alpha-induced release of cytokines from purified human blood eosinophils. Clin Mol Allergy. 2005;3:5–9.

    Article  PubMed  Google Scholar 

  24. Sorbera LA, Martin L, Leeson PA. Treatment of IBD: anti-TNF-α MAb. Drugs Future. 2000;25:669–73.

    Article  CAS  Google Scholar 

  25. Kang BS, Chung EY, Yun YP, Lee MK, Lee YR, Lee KS, et al. Inhibitory effects of anti-inflammatory drugs on interleukin-6 bioactivity. Biol Pharm Bull. 2001;24:701–3.

    Article  PubMed  CAS  Google Scholar 

  26. Escotte S, Tabary O, Dusser D, Teboul CM, Puchelle E, Jacquot J. Fluticasone reduces IL-6 and IL-8 production of cystic fibrosis bronchial epithelial cells via IKK-β kinase pathway. Eur Respir J. 2003;21:574–81.

    Article  PubMed  CAS  Google Scholar 

  27. Smirnov IM, Bailey K, Flowers CH, Garrigues NW, Wesselius LJ. Effects of TNF-α and IL-1β on iron metabolism by A549 cells and influence on cytotoxicity. Am J Physiol. 1999;277:L257–63.

    PubMed  CAS  Google Scholar 

  28. Toogood JH, Baskerville J, Jennings B, Lefcoe NM, Johansson SA. Bioequivalent doses of budesonide and prednisone in moderate and severe asthma. J Allergy Clin Immunol. 1989;84:688–700.

    Article  PubMed  CAS  Google Scholar 

  29. Kamada AK, Szefler SJ, Martin RJ, Boushey HA, Chinchilli VM, Drazen JM, et al. Issues in the use of inhaled glucocorticoids. The Asthma Clinical Research Network. Am J Respir Crit Care Med. 1996;153:1739–48.

    PubMed  CAS  Google Scholar 

  30. Miyamoto T, Takahashi T, Nakajima S, Makino S, Yamakido M, Mano K. A double-blind, placebo-controlled dose-response study with budesonide Turbuhaler in Japanese asthma patients. Respirology. 2000;5:247–56.

    Article  PubMed  CAS  Google Scholar 

  31. Busse W, Chervinsky P, Condemi J, Lumry WR, Petty TL, Rennard S. Budesonide delivered by Turbuhaler is effective in a dose-dependent fashion when used in the treatment of adult patients with chronic asthma. J Allergy Clin Immunol. 1998;101:457–63.

    Article  PubMed  CAS  Google Scholar 

  32. van den Brink KI, Boorsma M, den Brekel AJ Staal-van, Edsbäcker S, Wouters EF, Thorsson L. Evidence of the in vivo esterification of budesonide in human airways. Br J Clin Pharmacol. 2008;66:27–35.

    Article  PubMed  CAS  Google Scholar 

  33. Edsbacker S, Brattsand R. Budesonide fatty-acid esterification: a novel mechanism prolonging binding to airway tissue. Review of available data. Ann Allergy Asthma Immunol. 2002;88:609–16.

    Article  PubMed  Google Scholar 

  34. Tronde A, Gillen M, Borgstrom L, Lotvall J, Ankerst J. Pharmacokinetics of budesonide and formoterol administered via 1 pressurized metered-dose inhaler in patients with asthma and COPD. J Clin Pharmacol. 2008;48:1300–8.

    Article  PubMed  CAS  Google Scholar 

  35. Joshi M, Misra A. Dry powder inhalation of liposomal ketotifen fumarate: formulation and characterization. Int J Pharm. 2001;223:15–27.

    Article  PubMed  CAS  Google Scholar 

  36. Shah SP, Misra A. Liposomal amikacin dry powder inhaler: effect of fines on in vitro performance. AAPS PharmSciTech. 2004;5:1–7.

    Article  Google Scholar 

  37. Naikwade SR, Meshram RN, Bajaj AN. Preparation and in vivo efficacy study of pancreatin microparticles as enzyme replacement therapy for pancreatitis. Drug Dev Ind Pharm. 2009;35:417–32.

    Article  PubMed  CAS  Google Scholar 

  38. Wakode R, Bhanushali R, Bajaj A. Development and evaluation of push–pull based osmotic delivery system for pramipexole. PDA J Pharm Sci Tech. 2008;62:22–31.

    CAS  Google Scholar 

  39. Amrutiya N, Bajaj A, Madan M. Development of microsponges for topical delivery of mupirocin. AAPS PharmSciTech. 2009;10:402–9. doi:10.1208/s12249-009-9220-7.

    Article  PubMed  CAS  Google Scholar 

  40. Naikwade SR, Kulkarni PP, Jathar SR, Bajaj AN. Development of time and pH dependent controlled release colon specific delivery of tinidazole. DARU. 2008;16:119–27.

    Google Scholar 

  41. Naikwade SR, Bajaj AN. Development and evaluation of once a day oral controlled multiparticulate drug delivery systems of cefixime trihydrate. Indian J Pharm Educ Res. 2008;42:283–94.

    Google Scholar 

  42. Patel V, Patel M, Patel R. Chitosan: a unique pharmaceutical excipient. Drug Deliv Technol. 2005;5(6). http://www.drugdeliverytech.com.

  43. Baxter A, Dillon M, Taylor KDA, Roberts GAF. Improved method for I.R. determination of the degree of N-acetylation of chitosan. Int J Biol Macromol. 1992;14:166–9.

    Article  PubMed  CAS  Google Scholar 

  44. Zijlstra GS, Rijkeboer M, Drooge DJ, Sutter M, Jiskoot W, Weert MV, et al. Characterization of a cyclosporine solid dispersion for inhalation. AAPS J. 2007;9:E190–9.

    Article  PubMed  Google Scholar 

  45. Huang YC, Chiang CH, Yeh MK. Optimizing formulation factors in preparing chitosan microparticles by spray-drying method. J Microencapsul. 2003;20:247–60.

    Article  PubMed  CAS  Google Scholar 

  46. Sebti T, Amighi K. Preparation and in vitro evaluation of lipidic carriers and fillers for inhalation. Eur J Pharm Biopharm. 2006;63:51–8.

    Article  PubMed  CAS  Google Scholar 

  47. Heng PWS, 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;48:393–8.

    PubMed  CAS  Google Scholar 

  48. Corrigan DO, Healy AM, Corrigan OI. Preparation and release of salbutamol from chitosan and chitosan co-spray dried compacts and multiparticulates. Eur J Pharm Biopharm. 2006;62:295–305.

    Article  PubMed  CAS  Google Scholar 

  49. Corrigan DO, Healy AM, Corrigan OI. The effect of spray drying solutions of bendroflumethiazide/polyethylene glycol on the physicochemical properties of the resultant materials. Int J Pharm. 2003;262:125–37.

    Article  PubMed  CAS  Google Scholar 

  50. Prinn KB, Costantino HR, Tracy M. Statistical modeling of protein spray drying at the lab scale. AAPS PharmSciTech. 2002;3:1–6.

    Article  Google Scholar 

  51. Hirst PH, Pitcairn GR, Weers JG, Tarara TE, Clark AR, Dellamary LA, et al. In vivo lung deposition of hollow porous particles from a pressurized metered dose inhaler. Pharm Res. 2002;19:258–64.

    Article  PubMed  CAS  Google Scholar 

  52. Ungaro F, Rosa GD, Miro A, Quaglia F, Rotonda MIL. Cyclodextrins in the production of large porous particles: development of dry powders for the sustained release of insulin to the lungs. Eur J Pharm Sci. 2006;28:423–32.

    Article  PubMed  CAS  Google Scholar 

  53. Skiba M, Bounoure F, Barbot C, Arnaud P, Skiba M. Development of cyclodextrin microspheres for pulmonary drug delivery. J Pharm Pharmaceut Sci. 2005;8:409–18.

    CAS  Google Scholar 

  54. Boer AHD, Hagedoorn P, Gjaltema D, Goede J, Frijlink HW. Air classifier technology (ACT) in dry powder inhalation part 1: introduction of a novel force distribution concept (FDC) explaining the performance of a basic air classifier on adhesive mixtures. Int J Pharm. 2004;260:187–200.

    Google Scholar 

  55. Cerchiara T, Luppi B, Chidichimo G, Bigucci F, Zecchi V. Chitosan and poly(methyl vinyl ether-co-maleic anhydride) microparticles as nasal sustained delivery systems. Eur J Pharm Biopharm. 2005;61:195–200.

    Article  PubMed  CAS  Google Scholar 

  56. Jain SK, Agrawal GP, Jain NK. Evaluation of porous carrier-based floating orlistat microspheres for gastric delivery. AAPS PharmSciTech. 2006;7:E1–9.

    Article  PubMed  Google Scholar 

  57. Naikwade SR, Bajaj AN. Development of validated specific HPLC method for budesonide and characterization of its alkali degradation product. Can J Anal Sci Spect. 2008;53:113–22.

    CAS  Google Scholar 

  58. Jansson AH, Eriksson C, Wang X. Effects of budesonide and N-acetylcysteine on acute lung hyperinflation, inflammation and injury in rats. Vascul Pharmacol. 2005;43:101–11.

    Article  PubMed  CAS  Google Scholar 

  59. Kouno T, Katsumata N, Mukai H, Ando M, Watanabe T. Standardization of the body surface area (BSA) formula to calculate the dose of anticancer agents in Japan. Jpn J Clin Oncol. 2003;33:309–13.

    Article  PubMed  Google Scholar 

  60. Landry ML, Cohen S, Huber K. Comparison of EDTA and acid-citrate-dextrose collection tubes for detection of cytomegalovirus antigenemia and infectivity in leukocytes before and after storage. J Clin Microbiol. 1997;35:305–6.

    PubMed  CAS  Google Scholar 

  61. Leung TF, Wong CK, Lam CWK, Li AM, Wong GWK, Fok TF. Plasma TARC concentration may be a useful marker for asthmatic exacerbation in children. Eur Respir J. 2003;21:616–20.

    Article  PubMed  CAS  Google Scholar 

  62. Baek M, Chung HS, Kim Y, Kim DH. Disposition and metabolism of 2-(2″(1″,3″-dioxolan-2-yl)-2-methyl-4-(2′-oxopyrrolidin-1-yl)-6-nitro-2h-1-benzopyran (Skp-450) in rats. Drug Metab Dispos. 1999;27:510–6.

    PubMed  CAS  Google Scholar 

  63. Kronkvist K, Gustavsson M, Wendel AK, Jaegfeldt H. Automated sample preparation for the determination of budesonide in plasma samples by liquid chromatography and tandem mass spectrometry. J Chromatogr. 1998;823:401–9.

    Article  CAS  Google Scholar 

  64. Deventer K, Mikulkova P, Hoecke HV, Eenoo PV, Delbeke FT. Detection of budesonide in human urine after inhalation by liquid chromatography–mass spectrometry. J Pharm Biomed Anal. 2006;42:474–9.

    Article  PubMed  CAS  Google Scholar 

  65. Kaiser H, Aaronson D, Dockhorn R, Edsbacker S, Korenblat P, Kallen A. Dose-proportional pharmacokinetics of budesonide inhaled via Turbuhaler. Br J Clin Pharmacol. 1999;48:309–16.

    Article  PubMed  CAS  Google Scholar 

  66. Faouzi MA, Dine T, Luyckx M, Brunet C, Gressier B, Cazin M, et al. High-performance liquid chromatographic method for the determination of budesonide in bronchoalveolar lavage of asthmatic patients. J Chromatogr. 1995;664:463–7.

    Article  CAS  Google Scholar 

  67. Larsson AM, Jansson P, Runström A, Brattsand R. Prolonged airway activity and improved selectivity of budesonide possibly due to esterification. Am J Respir Crit Care Med. 2000;162:1455–61.

    Google Scholar 

  68. Vyve TV, Chanez P, Lacoste JY, Bousquet J, Michel FB, Godard P. Comparison between bronchial and alveolar samples of bronchoalveolar lavage fluid in asthma. Chest. 1992;102:356–61.

    Article  PubMed  Google Scholar 

  69. Jendbro M, Johansson CJ, Strandberg P, Falknilsson H, Edsbacker S. Pharmacokinetics of budesonide and its major ester metabolite after inhalation and intravenous administration of budesonide in the rat. Drug Metab Dispos. 2001;29:769–76.

    PubMed  CAS  Google Scholar 

  70. Gandhi R, Kaul CL, Panchagnula R. Pharmacokinetic evaluation of an azithromycin controlled release dosage form in healthy human volunteers: a single dose study. Int J Pharm. 2004;270:1–8.

    Article  PubMed  CAS  Google Scholar 

  71. Lewis S, Subramanian G, Pandey S, Udupa N. Design, evaluation and pharmacokinetic study of mucoadhesive buccal tablets of nicotine for smoking cessation. Indian J Pharm Sci. 2006;68:829–31.

    Article  CAS  Google Scholar 

  72. Donnelly R, Seale JP. Clinical pharmacokinetics of inhaled budesonide. Clin Pharmacokinet. 2001;40:427–40.

    Article  PubMed  CAS  Google Scholar 

  73. Yadav PN, Liu Z, Rafi MM. A diarylheptanoid from lesser galangal (Alpinia officinarum) inhibits proinflammatory mediators via inhibition of mitogen-activated protein kinase, p44/42, and transcription factor nuclear factor-{kappa}B. J Pharmacol Exp Ther. 2003;305:925–31.

    Article  PubMed  CAS  Google Scholar 

  74. Henry JR, Rupert KC, Dodd JH, Turchi IJ, Wadsworth SA, Cavender DE, et al. Potent inhibitors of the MAP kinase p38. Bioorg Med Chem Lett. 1998;8:3335–40.

    Article  PubMed  CAS  Google Scholar 

  75. Wilson BMG, Severn A, Rapson NT, Chana J, Hopkins P. A convenient human whole blood culture system for studying the regulation of tumor necrosis factor release by bacterial lipopolysaccharide. J Immunol Methods. 1991;139:233–40.

    Article  PubMed  CAS  Google Scholar 

  76. Monn C, Becker S. Cytotoxicity and induction of proinflammatory cytokines from human monocytes exposed to fine (PM2.5) and coarse Particles (PM10-2.5) in outdoor and indoor air. Toxicol Appl Pharmacol. 1999;155:245–52.

    Article  PubMed  CAS  Google Scholar 

  77. Kompella UB, Bandi N, Ayalasomayajula SP. Subconjunctival nano- and microparticles sustain retinal delivery of budesonide, a corticosteroid capable of inhibiting VEGF expression. Invest Ophthalmol Vis Sci. 2003;44:1192–201.

    Article  PubMed  Google Scholar 

  78. Greenberg AK, Hu J, Basu S, Hay J, Reibman J, Yie T, et al. Glucocorticoids inhibit lung cancer cell growth through both the extracellular signal-related kinase pathway and cell cycle regulators. Am J Respir Cell Mol Biol. 2002;27:320–8.

    PubMed  CAS  Google Scholar 

  79. Fujitani Y, Trifilieff A. In vivo and in vitro effects of SAR 943, a rapamycin analogue, on airway inflammation and remodeling. Am J Respir Crit Care Med. 2003;167:193–8.

    Article  PubMed  Google Scholar 

  80. Newman SP, Pitcairn GR, Hirst PH, Rankin L. Radionuclide imaging technologies and their use in evaluating asthma drug deposition in the lungs. Adv Drug Deliv Rev. 2003;55:851–67.

    Article  PubMed  CAS  Google Scholar 

  81. Ball DJ, Hirst PH, Newman SP, Sonet B, Streel B, Vanderbist F. Deposition and pharmacokinetics of budesonide from the Miat Monodose inhaler, a simple dry powder device. Int J Pharm. 2002;245:123–32.

    Article  PubMed  CAS  Google Scholar 

  82. Pitcairn GR, Hooper G, Luria X, Rivero X, Newman SP. A scintigraphic study to evaluate the deposition patterns of a novel antiasthma drug inhaled from the Cyclohaler dry powder inhaler. Adv Drug Deliv Rev. 1997;26:59–67.

    Article  PubMed  CAS  Google Scholar 

  83. Bondesson E, Bengtsson T, Borgström L, Nilsson LE, Norrgren K, Trofast E, et al. Planar gamma scintigraphy—points to consider when quantifying pulmonary dry powder aerosol deposition. Int J Pharm. 2003;258:227–40.

    Article  PubMed  Google Scholar 

  84. Lee Z, Ljungberg M, Muzic RF, Berridge MS. Usefulness and pitfalls of planar γ-scintigraphy for measuring aerosol deposition in the lungs: a Monte Carlo investigation. J Nucl Med. 2001;42:1077–83.

    PubMed  CAS  Google Scholar 

  85. Bondesson E, Bengtsson T, Borgstrom L, Nilsson LE, Norrgren K, Trofast E, et al. Planar gamma scintigraphy—points to consider when quantifying pulmonary dry powder aerosol deposition. Int J Pharm. 2003;251:33–47.

    Article  PubMed  CAS  Google Scholar 

  86. Myers MJ, Lavender JP, Deoliviera JB, Maseri A. A simplified method of quantitating organ uptake using a gamma camera. Br J Radiol. 1981;54:1062–7.

    Article  PubMed  CAS  Google Scholar 

  87. Pitcairn GR, Newman SP. Tissue attenuation corrections in gamma scintigraphy. J Aerosol Med. 1997;10:187–98.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. C. U. Shah College of Pharmacy, S.N.D.T. Women’s University, Juhu-Tara Road, Santacruz (W), Mumbai, 400049, Maharashtra, India

    Sonali R. Naikwade & Amrita N. Bajaj

  2. Department of Pharmacology and Toxicology, Bombay Veterinary College, Parel, Mumbai, 400 012, India

    Prashant Gurav & Madhumanjiri M. Gatne

  3. Medical Cyclotron Project, LNMS, BARC, Medical Cyclotron Facility, BRIT, Tata Memorial Centre Annex, E. Borges Marg, Parel, Mumbai, 400012, India

    Pritam Singh Soni

Authors
  1. Sonali R. Naikwade
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amrita N. Bajaj
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Prashant Gurav
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Madhumanjiri M. Gatne
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pritam Singh Soni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amrita N. Bajaj.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Naikwade, S.R., Bajaj, A.N., Gurav, P. et al. Development of Budesonide Microparticles Using Spray-Drying Technology for Pulmonary Administration: Design, Characterization, In Vitro Evaluation, and In Vivo Efficacy Study. AAPS PharmSciTech 10, 993–1012 (2009). https://doi.org/10.1208/s12249-009-9290-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-009-9290-6

Key words

Search

Navigation