Review on Week 6 Lecture

Review on Week 6 Lecture

Particle Based Drug Delivery System

Delivery ProblemsThere are several problem in delivering drugs to

humans High dose or high frequency of dose Patient discomfort or rejection of drug Objective: to kill cancer/undesired cells without

killing other non-cancer/useful cells Example: To avoid over dosage

Plasma Drug Concentration Profile This profile is important because it

shows the maximum limit, controlled release and minimum limit which is base on:

Minimum effective level: prevention of material wastage

Maximum effective level: prevention of increasing risk

Techniques introduced to achieve sustainable release eg by compressed tablets

HOWEVER….problems still exist Amount of drug released

depends on patients conditions Environmental effects Repeated dosage required

Controlled Polymeric Delivery System

Advantages Less expensive Less wastage of

material used Reduce side effects

which are harmful

Disadvantages Sometimes can be

expensive Sometimes can

produce harmful by-products if its biodegradable

Lack of biocompatibility

Diffusion(Commonly used)

Reservoirs Surrounded by polymer films Diffusion of drug via rate

limiting step E.g membranes or capsules Polymer used like silicone

rubber Disadvantages are its

expensive and rapid release Able to achieve “zero” order

kinetics

Types of Controlled Drug Release Polymeric System

At Time= 0

At Time= t

Types of Controlled Drug Release Polymeric System

Matrices Uniformly distributed Diffusion of drug via rate

limiting step Not generally “zero” order

At Time= 0

At Time= t

Chemically Controlled System

Bioerodible Distributed uniformly like

matrices Polymer degrades with time

and release drug at the same time

At Time= 0

At Time= t

Chemically Controlled SystemPendant Chain

Chemically bound to polymer backbone chain

Released by hydrolytic/enzymatic cleavage

Degrades by hydrolytic Heterogeneous degradation:

Occurs at carrier surface Constant degradation rate Chemically integrity retained in smaller

portion Homogeneous degradation

Random cleavage throughout polymer bul Molecular Weight decreases steadily At critical MW, solubilisation and mass

loss happens

At Time= 0

At Time= t

Swelling Controlled System

Using glass or rubbery state polymer

Drug dissolved or dispersed in polymer

Dissolution medium penetrates matrix and swells the backbone

When swollen polymer in rubbery state, drug diffusion occurs

At Time= 0

At Time= t

Magnetically Controlled System

Drug and small magnetic beads dispersed in polymer matrix

Upon medium exposure, release like matrix system

Upon exposure to oscillating external magnetic field, more release rate

At Time= 0

At Time= tOscillating magnetic field

Types of polymers used in drug release

Hydrophilic Polymers Tendency to interact or dissolved by water Reservoir and monolithic devices prepared from swollen cross-linked hydrophilic

polymers Eg PVA (Poly Vinyl Alcohol)

Hydrophobic Polymers Repels water Polymer available as uncross-linked matrices or membranes Eg EVAC ( Ethylene Vinyl Acetate)

Biodegradable Polymers Degrades over time Eg PLA (PolyLactic Acid)

Fabrication of drug delivery devices

Tutorial 7Present to you by group 1

Overview

Electro-spinning Electrodynamic Atomization-EHDA Supercritical Antisolvent with enhance mass transfer- (SAS-ME)

Electro-spinning

Electro spinning uses an electrical charge (high voltage) to draw very fine (typically on the micro or nano scale) fibres from a liquid.

• Fabricating poly(lactic-co-glycolic acid)-PLGA microfiber.• Size range from 3nm to more than 5 microns.

Diagram of a electro spinning

Parameter that affect the formation and structure of produced nanofibers

1. SOLUTION Viscosity Solution concentration Molecular weight of the polymer Solvent properties Surface tension Conductivity

Parameter that affect the formation and structure of produced nanofibers

2. PROCESS– Voltage applied– Distance of the electrode from the collector– Flow rate– Capillary geometry

3. ENVIRONMENT– Temperature– Relative humidity

Effects of controlling parameter on fiber diameter

Electrodynamic Atomization(EHDA)

Similar to electro spinning, EDHA applies electrical stress (high voltage) on the fluid that emerges from the tip of the nozzle, which forms a Taylor cone that decreases the diameter of the jet.• Fabricating paclitaxel-loaded PCL/PLGA micro particles• Particle sizes ranges in micron scale

Diagram of a EHDA set-up

Parameter that affect the formation and structure of produced Micro Particle

1. SOLUTION– Viscosity– Solution concentration– Molecular weight of the polymer– Solvent properties– Surface tension– Conductivity

2. PROCESS– Voltage applied– Flow rate– Capillary geometry

Supercritical Antisolvent with enhance mass transfer- (SAS-ME)

SAS supercritical antisolvent SAS supercritical antisolvent with enhanced mass transfer

Supercritical Antisolvent with enhance mass transfer- (SAS-ME)

SAS• Uses CO2 as an anti-solvantThe advantages of supercritical fluid processing include mild operating temperatures, production of solvent free particles and easy micro encapsulation of particles.• The operating temperature, pressure and concentration of the

injecting solution have so far been investigated as size control parameters, but none of these parameters have been found to produce a significant decrease in the particle size over a wide range.

• Therefore it is unable to produce fine particles in the sub-micron range (<300 nm)

Supercritical Antisolvent with enhance mass transfer- (SAS-ME)

SAS-ME• Use supercritical carbon dioxide as the anti solvent• Utilizes a surface, vibrating at an ultrasonic frequency to atomize the

solution jet into micro-droplets. Moreover, the ultrasound field greatly enhances turbulence and mixing within the supercritical phase resulting in high mass transfer between the solution and the antisolvent.

• The combined effect of fast rate of mixing between the antisolvent and the solution, and reduction of solution droplet size due to atomization, provides particles approximately ten-fold smaller than those obtained from the conventional SAS process.

• Able to produce particles in the nanometer range having a very narrow size distribution.

Supercritical Antisolvent with enhance mass transfer- (SAS-ME)

Results of the precipitation experiments conducted using the SASEM technique at 96.5 bar, 37 degreeC and at different values of ultrasound power supply, for various pharmaceutical compounds, have been shown below.

Source: http://www.isasf.net/fileadmin/files/Docs/Versailles/Papers/Md3.pdf

Conclusion

Advantages of nano particle drug delivery system:1. improved bioavailability by enhancing aqueous solubility2. increasing resistance time in the body(sustained release of drug)3. targeting drug to specific location in the body (its site of action).This results in concomitant reduction in quantity of the drug required and dosage toxicity, enabling the safe delivery of toxic therapeutic drugs and protection of non target tissues and cells from severe side effects.

Fabrication of drug delivery devices

Tutorial 7Present to you by group 1

Overview

• Electro-spinning • Electrodynamic Atomization-EHDA• Supercritical Antisolvent with enhance mass transfer- (SAS-ME)

Electro-spinning

Electro spinning uses an electrical charge (high voltage) to draw very fine (typically on the micro or nano scale) fibres from a liquid.

• Fabricating poly(lactic-co-glycolic acid)-PLGA microfiber.• Size range from 3nm to more than 5 microns.

Diagram of a electro spinning

Parameter that affect the formation and structure of produced nanofibers

1. SOLUTION– Viscosity– Solution concentration– Molecular weight of the polymer– Solvent properties– Surface tension– Conductivity

Parameter that affect the formation and structure of produced nanofibers

2. PROCESS– Voltage applied– Distance of the electrode from the collector– Flow rate– Capillary geometry

3. ENVIRONMENT– Temperature– Relative humidity

Effects of controlling parameter on fiber diameter

Electrodynamic Atomization(EHDA)

Similar to electro spinning, EDHA applies electrical stress (high voltage) on the fluid that emerges from the tip of the nozzle, which forms a Taylor cone that decreases the diameter of the jet.• Fabricating paclitaxel-loaded PCL/PLGA micro particles• Particle sizes ranges in micron scale

Diagram of a EHDA set-up

Parameter that affect the formation and structure of produced Micro Particle

1. SOLUTION– Viscosity– Solution concentration– Molecular weight of the polymer– Solvent properties– Surface tension– Conductivity

2. PROCESS– Voltage applied– Flow rate– Capillary geometry

Supercritical Antisolvent with enhance mass transfer- (SAS-ME)

SAS supercritical antisolvent SAS supercritical antisolvent with enhanced mass transfer

Supercritical Antisolvent with enhance mass transfer- (SAS-ME)

SAS• Uses CO2 as an anti-solvantThe advantages of supercritical fluid processing include mild operating temperatures, production of solvent free particles and easy micro encapsulation of particles.• The operating temperature, pressure and concentration of the injecting solution have so far been investigated as

size control parameters, but none of these parameters have been found to produce a significant decrease in the particle size over a wide range.

• Therefore it is unable to produce fine particles in the sub-micron range (<300 nm)

Supercritical Antisolvent with enhance mass transfer- (SAS-ME)

SAS-ME• Use supercritical carbon dioxide as the anti solvent• Utilizes a surface, vibrating at an ultrasonic frequency to atomize the solution jet into micro-droplets. Moreover,

the ultrasound field greatly enhances turbulence and mixing within the supercritical phase resulting in high mass transfer between the solution and the antisolvent.

• The combined effect of fast rate of mixing between the antisolvent and the solution, and reduction of solution droplet size due to atomization, provides particles approximately ten-fold smaller than those obtained from the conventional SAS process.

• Able to produce particles in the nanometer range having a very narrow size distribution.

Supercritical Antisolvent with enhance mass transfer- (SAS-ME)

Results of the precipitation experiments conducted using the SASEM technique at 96.5 bar, 37 degreeC and at different values of ultrasound power supply, for various pharmaceutical compounds, have been shown below.

Source: http://www.isasf.net/fileadmin/files/Docs/Versailles/Papers/Md3.pdf

Conclusion

Advantages of nano particle drug delivery system:1. improved bioavailability by enhancing aqueous solubility2. increasing resistance time in the body(sustained release of drug)3. targeting drug to specific location in the body (its site of action).This results in concomitant reduction in quantity of the drug required and dosage toxicity, enabling the safe delivery of toxic therapeutic drugs and protection of non target tissues and cells from severe side effects.