AAPS PharmSciTech

, Volume 10, Issue 3, pp 993–1012

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

  • Sonali R. Naikwade
  • Amrita N. Bajaj
  • Prashant Gurav
  • Madhumanjiri M. Gatne
  • Pritam Singh Soni
Research Article

DOI: 10.1208/s12249-009-9290-6

Cite this article as:
Naikwade, S.R., Bajaj, A.N., Gurav, P. et al. AAPS PharmSciTech (2009) 10: 993. doi:10.1208/s12249-009-9290-6

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, Tmax, Cmax, 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 T1/2 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 vitroin 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.

Key words

budesonide dry powder inhaler gamma scintigraphy microparticles spray drying 

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

Copyright information

© American Association of Pharmaceutical Scientists 2009

Authors and Affiliations

  • Sonali R. Naikwade
    • 1
  • Amrita N. Bajaj
    • 1
  • Prashant Gurav
    • 2
  • Madhumanjiri M. Gatne
    • 2
  • Pritam Singh Soni
    • 3
  1. 1.C. U. Shah College of PharmacyS.N.D.T. Women’s UniversityMumbaiIndia
  2. 2.Department of Pharmacology and ToxicologyBombay Veterinary CollegeMumbaiIndia
  3. 3.Medical Cyclotron Project, LNMS, BARCMedical Cyclotron Facility, BRIT, Tata Memorial Centre AnnexMumbaiIndia