Effect of chemical conjugation of L-leucine to chitosan on the dispersibility and drug release of a dry powder inhaler nanoparticle formulation

Muhsin, Mohammad, George, Graeme, Beagley, Kenneth, Ferro, Vito, & Islam, Nazrul (2013) Effect of chemical conjugation of L-leucine to chitosan on the dispersibility and drug release of a dry powder inhaler nanoparticle formulation. In American Association for Pharmaceutical Scientist (AAPS) Annual Meeting and Exposition 2013, 10-14 November 2013, San Antonio, Texas, USA. (Unpublished)

Abstract

Purpose: This study investigated the effect of chemical conjugation of the amino acid L-leucine to the polysaccharide chitosan on the dispersibility and drug release pattern of a polymeric nanoparticle (NP)-based controlled release dry powder inhaler (DPI) formulation.

Methods: A chemical conjugate of L-leucine with chitosan was synthesized and characterized by Infrared (IR) Spectroscopy, Nuclear Magnetic Resonance (NMR) Spectroscopy, Elemental Analysis and X-ray Photoelectron Spectroscopy (XPS). Nanoparticles of both chitosan and its conjugate were prepared by a water-in-oil emulsification – glutaraldehyde cross-linking method using the antihypertensive agent, diltiazem (Dz) hydrochloride as the model drug. The surface morphology and particle size distribution of the nanoparticles were determined by Scanning Electron Microscopy (SEM) and Dynamic Light Scattering (DLS). The dispersibility of the nanoparticle formulation was analysed by a Twin Stage Impinger (TSI) with a Rotahaler as the DPI device. Deposition of the particles in the different stages was determined by gravimetry and the amount of drug released was analysed by UV spectrophotometry. The release profile of the drug was studied in phosphate buffered saline at 37 ⁰C and analyzed by UV spectrophotometry.

Results: The TSI study revealed that the fine particle fractions (FPF), as determined gravimetrically, for empty and drug-loaded conjugate nanoparticles were significantly higher than for the corresponding chitosan nanoparticles (24±1.2% and 21±0.7% vs 19±1.2% and 15±1.5% respectively; n=3, p<0.05). The FPF of drug-loaded chitosan and conjugate nanoparticles, in terms of the amount of drug determined spectrophotometrically, had similar values (21±0.7% vs 16±1.6%). After an initial burst, both chitosan and conjugate nanoparticles showed controlled release that lasted about 8 to 10 days, but conjugate nanoparticles showed twice as much total drug release compared to chitosan nanoparticles (~50% vs ~25%). Conjugate nanoparticles also showed significantly higher dug loading and entrapment efficiency than chitosan nanoparticles (conjugate: 20±1% & 46±1%, chitosan: 16±1% & 38±1%, n=3, p<0.05).

Conclusion: Although L-leucine conjugation to chitosan increased dispersibility of formulated nanoparticles, the FPF values are still far from optimum. The particles showed a high level of initial burst release (chitosan, 16% and conjugate, 31%) that also will need further optimization.

Impact and interest:

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ID Code: 66486
Item Type: Conference Item (Poster)
Refereed: Yes
Additional URLs:
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > PHARMACOLOGY AND PHARMACEUTICAL SCIENCES (111500)
Divisions: Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > Schools > School of Clinical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2013 Please consult the authors
Deposited On: 22 Jan 2014 01:13
Last Modified: 22 Jan 2014 01:14

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