Particles for controlled drug delivery

Tomasz Ciach 

Warsaw University of Technology, Faculty of Chemical Engineering, Warynskiego 1, Warsaw 00-645, Poland

Abstract

The number on newly registered pharmaceutical active entities is slowly decreasing over the last two decades, despite the constant increase of spending on the research. On the other hand the societies are getting older and the demand for new efficient and convenient therapies is growing. One way to solve this problem is to make a better use of existing, already know substances. It can be done by the development of new encapsulation and delivery methods for active substances. Encapsulation of a drug can efficiently modify its pharmacokinetic and can deliver the drug molecules to the desired area, and release it in the desired manner. To achieve that, the drugs are encapsulated in biodegradable or biocompatible polymers, sometimes equipped in targeting molecules. The majority of particles, used for controlled release of medicine are obtained by wet chemistry techniques, mostly by different types of emulsification and emulsion polymerisation processes. This offers many advantages like high volumetric production rates and simplicity of the process. The wet route is however not capable to fulfil all requirements with respect to different types of polymers and surface chemistries. Also the efficiency of encapsulation of the active compound is not always high in the wet methods. An alternative way to the wet route for the production of drug containing particles is the aerosol route. This group of techniques is also a natural choice for drug delivery via inhalation.

This paper shows a possibility of applying of the Electro Hydro Dynamic Atomisation (EHDA) for the production of biodegradable particles for controlled drug delivery. EHDA or electrospraying is a versatile and gentle method to atomise liquids. It allows the production of particles with a narrow size distribution with an easy way to tune to a desired size. Particles with a wide variety of chemical compositions can be made this way. As a precursor for particles virtually each compound that dissolves in a suitable liquid can be used. Generally EHDA refers to a process, where a liquid jet breaks up into droplets under the influence of electrical forces. Depending on the strength of the electric stresses in the liquid surface relative to the surface tension different spraying modes will be obtained. For the production of pharmaceutical micro particles the so called cone-jet mode seems to be the most promising. In this mode a liquid is pumped through a nozzle at a low flow rate. An electric field of sufficient strength is applied over the nozzle and some counter electrode and the droplet at the nozzle is transformed into a conical shape, from the apex of which a jet emerges. This liquid jet breaks up into small droplets due to hydrodynamic instabilities. After solvent evaporation droplets forms mono dispersed particles sized from nanometers up to tens of micrometers.  Standard deviation of particle sizes is usually in the range of 1.15 – 1.2. EHDA method of particles productions is very gentle so even vulnerable peptides survive the atomisation process. Diameter of particles obtained by EHDA can vary from tens of nanometrs to hundreds of micrometers. Smallest particles can be applied in targeted drug delivery for cancer treatment while biggest as long term slow release particles for intramuscular delivery. Smallest are able to carry the drug for few hours only, but can accumulate in the cancer area. Biggest degrade slowly and can release the drug for 4-8 weeks. Particles of about 100 micrometer diameter made of hydrogell of heavy chelating properties can serve as biodegradable radioactive isotope container for local cancer treatment.

Typical EHDA setup is presented in the picture below.

 Spray.jpg

Spraying nozzle is supplied with the particles precursor solution and connected to the high voltage power supply. Below the nozle a stabilising ring connected to intermidiate voltage is placed. Particles are collected on the grounded metal plate below.

 Example of drug containing particles obtained in the EHDA setup operating in the microdripping mode is shown in the picture below.

czastki.jpg

 Presented particles containes Risperidon which is released, after immersion in water, for about 8 weeks.

 

 

 

 

 

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Presentation: Invited oral at VII Multidyscyplinarna Konferencja Nauki o Leku, by Tomasz Ciach
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-02-05 20:49
Revised:   2010-03-06 10:41
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