1 / 17

Controlled drug delivery

Controlled drug delivery. Jonathan O’Dwyer John Rasmussen CHEN 641. Overview. Normal Application. Controlled Application. Chitosan in controlled drug delivery. History Structure and chemistry Properties Applications Controlled Drug Delivery. Overview. History.

howard-avery
Download Presentation

Controlled drug delivery

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Controlled drug delivery Jonathan O’Dwyer John Rasmussen CHEN 641

  2. Overview Normal Application Controlled Application

  3. Chitosan in controlled drug delivery • History • Structure and chemistry • Properties • Applications • Controlled Drug Delivery

  4. Overview

  5. History • Natural polysaccharide found in shells of crustaceans • Discovered in 1859 by Rouget • Chemical structure identified in 1950

  6. Structure and chemistry • Repeat Unit: b 1-4 N-glucosamine (~ 90%) b 1-4 N-acetylglucosamine (~ 10%) • Protonated amino groups at pH < 6.5 (NH3+) • Undergoes homogeneous reactions typical to amines (acylation and Schiff reactions) • Characterized by degreee of deacetylation (DD)

  7. Properties • Soluble at pH < 6.5 • Polycation (protonated amino groups) • Hydrophilic • Low toxicity • Biocompatible • Bioadhesive • Biodegradable • Enzymes present within the large intestines

  8. Applications • Wastewater (removal of metal ions) • Medical (wound dressing) • Health (weightloss supplement) • Membrane (permeability control) • Pharmaceutical (controlled drug delivery)

  9. Controlled Drug Delivery • Delivery form • Powder • Solution • Microparticle (50nm-2mm) • Delivery system • Oral • Injectable • Transdermal • Nasal

  10. Nasal drug delivery obstacles • aMembrane Permeability • Respiratory epithelium • Mucus layer (viscoelastic gel ~ 15mm) • Dense cilia tubules (200/cell) • Goblet cells • bResidence time (typically 10 min) • Mucociliary clearance (MCM) • Amount of mucus • Viscoelastic properties of the mucus • Cilia length, density, and beating frequency

  11. Overcoming obstacles • aPermeability enhancing polymers • Transiently opens paracellular transport pathway • bMicroparticlemucoadhesive polymers • Hydrogen or ionic bonding • Increase residence time (5 hrs & longer) • Increase bioavailability

  12. Chitosan drug release mechanism • Mucoadhesion/Ionic Binding • (+) interacts (-) cell membrane, decreasing MCM ~90% (i.e. increased residence time) • Swelling (hydrophilic) • Increases fluid within matrix forming a gel diffusion layer • Diffusion • Drug passes from the polymer matrix into the external environment

  13. Morphine phase II clinical trial • Pain treatment of cancer patients • Utilizes chitosan microparticles (20-30 mm) loaded with morphine • Microparticles delivered intranasally as powder formulation

  14. Morphine phase II clinical trial • Chitosan microparticle preparation (ChiSysTM) • Chitosan & morphine dissolved in DI-water • Droplets extruded into mineral oil (oil phase) • Emulsify aqueous phase into oil phase • Evaporate aqueous phase (heat forms crosslink) • Separate microparticles from oil phase by centrifugation

  15. Morphine phase II clinical trial • Mathematical modelling • Three models tested • Zero order • First order • Higuchi model (R2 = 0.999) • Describes release from a matrix • Q = k*t1/2 where: Q = amount of drug released per unit area of matrix

  16. Morphine phase II clinical trial • Results • Biphasic pattern • Initial phase • Rapid release • B/C drug on surface and particle defects • Terminal phase • Controlled release • Bioavailability of 70% compared to IV injection • 90% reduction in MCM • 99% of morphine delivered • Non-toxic

  17. Chitosan limitations (+) charged drug repelled by chitosan’s (+) charge • Low encapsulation efficiency for certain drugs due to repulsive forces • Soluble at pH < 6.5 • Highly refined chitosans required

More Related