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Review on Week 6 Lecture Particle Based Drug Delivery System.

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Presentation on theme: "Review on Week 6 Lecture Particle Based Drug Delivery System."— Presentation transcript:

1 Review on Week 6 Lecture Particle Based Drug Delivery System

2 Delivery Problems There 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

3 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

4 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

5 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

6 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

7 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

8 Chemically Controlled System Pendant 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

9 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

10 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= t Oscillating magnetic field

11 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)

12 Fabrication of drug delivery devices Tutorial 7 Present to you by group 1

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

14 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.

15 Diagram of a electro spinning

16 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

17 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

18 Effects of controlling parameter on fiber diameter

19 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

20 Diagram of a EHDA set-up

21 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

22 Supercritical Antisolvent with enhance mass transfer- (SAS-ME) SAS supercritical antisolventSAS supercritical antisolvent with enhanced mass transfer

23 Supercritical Antisolvent with enhance mass transfer- (SAS-ME) SAS Uses CO2 as an anti-solvant The 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)

24 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.

25 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:

26 Conclusion Advantages of nano particle drug delivery system: 1. improved bioavailability by enhancing aqueous solubility 2. 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.

27 Fabrication of drug delivery devices Tutorial 7 Present to you by group 1

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

29 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.

30 Diagram of a electro spinning

31 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

32 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

33 Effects of controlling parameter on fiber diameter

34 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

35 Diagram of a EHDA set-up

36 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

37 Supercritical Antisolvent with enhance mass transfer- (SAS-ME) SAS supercritical antisolventSAS supercritical antisolvent with enhanced mass transfer

38 Supercritical Antisolvent with enhance mass transfer- (SAS-ME) SAS Uses CO2 as an anti-solvant The 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)

39 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.

40 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:

41 Conclusion Advantages of nano particle drug delivery system: 1.improved bioavailability by enhancing aqueous solubility 2.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.


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