Development of optimally controlled drug release device using
Transcript of Development of optimally controlled drug release device using
Development of optimally controlled drug release
device using multi-layered electro-active nano-
polymersProject Guide:
Prof. Kajari KarguptaDept. Of Chemical Engineering
Jadavpur University
Dr. Saptarshi MajumdarDept. Of Chemical Engineering
Indian Institute Of Technology Hyderabad
Aim of the ProjectDevelopment of Smart Device : An
electro-active Polymer based drug delivery device
SIGNIFICANCE OF DRUG DELIVERY SYSTEM
Lower side effects Higher affectivity and higher bioavailability of
medicines closed to the affected portion of the body. Abandoned product
Multiple drugs in one shot
Lower required medical attention for patients
Commercial success can be found in following therapeutic categories:
Asthma Pain Management Cardiovascular Disease Dermatological Women’s Health
Medicines ApplicationsDexamethasone Neuro Inflammations
Dopamine NeurotransmitterSodium Salisylate Liver treatment
ATP Stimulator
CONDUCTING POLYMERS
An immobilizing medium that facilitate electron transfer as a result of the occurrence of an extensively delocalized -molecular orbital system in its structure
They exhibit the behavior of metals or semi-conductors (low excitation energy)
The random dispersion or aggregation of dopants in molar concentrations in the disordered chain like structure of polymers is called “Doping”
Low and intermediate stages of doping are observed as doping proceeds and polaron and bipolaron structures are formed.
Depending upon the various oxidation states they are classified into Emeraldine, Leucoemeraldine and Pernigraniline states(base or salt)
DIFFERENT OXIDATION STATES OF POLYANILINE
Only emeraldine (salt) is conductive
IMPORTANCE OF PANI AS A CONDUCTING POLYMERS
PANI having protonation, deprotonation and various other physico-chemical properties due to the presence of this -NH- group.
Inexpensive monomer, easy synthesis , environmental stability , simple doping by protonic acids .
PANI salt is quite stable and shows relatively high level of conductivity .
When treated with base the conducting PANI salt converts to the base form.
Electronic structure and electrical properties reversibly controlled by both oxidation and protonation .
OBJECTIVES :
Deposition of single and multi-layer thin film (electro-active polymer)
Studies on transport of ionic drug through polymeric film under applied time varying electric field.
Design a miniaturized capsule with a polymer membrane coating for the targeted and controlled release of anionic drugs essential for therapeutic activity.
Methodology:
Electrodeposition of conducting polymer membrane
=ELECTROCHEMICAL DEPOSITION: Two electrode system:
Cathode 25 mm Circular porous Stainless Steel plate(200 mesh)
Anode Graphite block
Sonication time(Ultra Sonicator: Piezo U Sonic):
2 hrs for PANI-p-TSA solution
30 minutes for PANI-p-TSA+ Dopant solution
Voltage: 30 volts,20 volts,10 volts (Voltage source: Testronics 92D)
Duration of electrodeposition: 1 hrs,2 hrs,4 hrs
Synthesis of conducting polymer :
ELECTRODEPOSITING SETUP
Testronics Voltage Source
Polymer membrane
Characterization of Conducting Polymer membrane
Scanning Electron Micrograph (SEM)
PANI(salt)-p-TSA
50 µm
100 µm
Transmission Electron Microscopy
PANI(base)-p-TSA
X-Ray Diffraction
0 10 20 30 40 50 60 700
100
200
300
400
500In
tens
ity(c
ps)
2 theta (degrees)
2d sin θ = n λ
Studies on transport of ionic drug through polymeric film under
applied time varying electric field.
Mechanism of Drug Release
Voltage (Positive Scan)
+
+
+
- +
- +
- +
-
-
-
Voltage (Negative Scan)
-
-
-
I
V
Porous BaseCP Film: Modified Working
Electrode
Counter Electrode
Permeate Side
Feed Side
Schematic Diagram of Experimental setup for Drug Release Study
DRUG RESERVOIR (A)
MEM
BR
AN
E
BODY FLUID (B)
PORO
US S
ILVE
R PL
ATE
L1=10cm
4cm
L2=5cm
2.5c
m
COMPUTER
RE
SAMPLE WITHDRAWING
A/D CONVERTER
4.290
OPENING SLOTWECE
meshGas cade
ONLINE pH and Conductivity measurement
PorousSilver plate
ID 2.5cm
OfflineUV-VIS
Spectrophotometer
Drug Delivery Experimental Set up
Platinum mesh (CE)Platinum mesh (CE)
COMPONENTS OF DRUG DELIVERY SET UPPolymer membrane(WE)
Gold thread (RE)
An electrode reaction refers to the net oxidation or reduction process that takes place at an electrode. This reaction may take place in a single electron-transfer step, or as a succession of two or more steps. The substances that receive and lose electrons are called the electroactive species
Three Electrode System
The major advantages of using a reference electrode are:
It is easy to prepare and maintain, and its potential is stable
During an electrode reaction involving a saturated solution of an insoluble salt of the ion, it helps in maintaining a fixed
concentration of an ionic species
Decrease of the effectiveness of the reference
electrode to stabilize working electrode voltage.
A resistance towards ion flow between the counter
and working electrodes, creating current dependent
voltage discrepancies due to IR drops
Disadvantages of Three Electrode System :
Type of Experimentations
1. Release characteristics from pre-loaded film (with drug) using a single compartment:
(i) In absence of feed solution
2. Experimentation on release characteristics using two compartment (feed and permeate side) module
(ii) OCP run: Study on diffusion characteristic with no applied voltage
(ii) Release due to Step potential
(iii) Release induced by Cyclic Voltammetry
Release pattern of para- toluene- sulfonic acid through Polyaniline (PANI) salt membrane in single compartment:
Details of experimentation for Polyaniline membrane: Membrane :
• PANI (salt) (24 mg) +NN-DMF(40 ml) sonicated for 2hr.• P-TSA as dopant (240 mg) sonicated for 30 mins .
Electro Deposition: Potential (V) = 30V
Duration=2hr Current Variation =0.09A
Drug Delivery Cell data:
Duration of experiment= 1hr We wanted to generate a step response in the cell
by giving the following target voltages and time in the Auto lab:
Voltage applied : -0.25V wrt RE
RESULT:
0 1000 2000 3000 4000 50000.00
0.02
0.04
0.06
0.08
0.10
Con
cent
ratio
n(M
)
Time(secs)
Source(V)
Time(sec)
-0.25 4500
In this case the concentration vs. time shows almost a linear profile which signifies the zero order release characteristics.
The average release rate estimated for PANI is 0.3 μmole/s
Experimentation on release characteristics using two compartment (feed and permeate side) module.
Case Study I: Stability analysis of PANI –PTSA (OCP run)
• Open Circuit Potential: for 28hrs
• Deposition: 30 mg PANI salt +50 ml NN,DMF +300 mg pTSA 30 volts & 0.09 amps for 2 hrs.
• Feed side: 0.1(M) PTSA solution.
• Permeate side: Water.
• Release due to Diffusion
Permeate side concentration (M) vs. Time (min)
CASE STUDY II: RELEASE CHARACTERISTICS OF PTSA AND SSA THROUGH PANI USING STEP VOLTAGE WRT RE
Details of experimentation for PTSA-PANI:
Membranei) PANI (salt) (30 mg) +NN-DMF(50 ml)
sonicated for 2hr. ii) P-TSA as dopant (300 mg)
sonicated for 30 mins.
Electro Deposition
Potential (V) = 30VDuration=2hr
Current Variation =0.08A
Drug Delivery Cell dataDuration of experiment= 150min
Open Circuit Potential: (for 600sec)
Feed side: 0.1(M) P-TSA solution.Permeate side: Distilled Water.
Details of experimentation for SSA-PANI:
Membranei) PANI (salt) (80 mg) +NN-DMF(50 ml)
sonicated for 2hr. (ii)SSA as dopant (300 mg)
sonicated for 30 mins.
Electro Deposition
Potential (V) = 30VDuration=2hr
Current Variation =0.08A
Drug Delivery Cell dataDuration of experiment= 150min
Open Circuit Potential: (for 600sec)
Feed side: 0.1(M) SSA solution.Permeate side: Distilled Water.
Results of Step Voltammetry
Release characteristics of PTSA through PANI-salt membrane using Cyclic Voltammetry
Run OCP(Volt)
Conc. Of Feed(M)
Scan Rate(Volt/Sec)
Flux(mol/sec m2)
Leakage(mol)
4 -0.027 0.05 0.0001 1.099E-4 2.088E-51 -0.242 0.05 0.004 2.93E-5 5.814E-62 -0.330 0.05 0.005 2.589E-4 6.6E-63 -0.283 0.1 0.005 2.102E-4 3.034E-65 -0.294 0.15 0.005 1.132E-4 4.34E-6
Comparison Curve :
EFFECT ON FLUX AT DIFFERENT SCAN RATEScan Rate (0.0002v/s )
Scan Rate (0.002v/s)Scan Rate (0.004v/s )
Voltage
(v)
Flux
(mol/sec m2)
Voltage
(v)
Flux
(mol/sec m2)
Voltage
(v)
Flux
(mol/sec m2)
0
0.4
0.8
0.4
0
0
9.372E-5
3.8808E-4
0
0.176
0.434
0.8
0.61
0.4
0.23
0
0
2.7732E-3
2.465E-3
0
2.598E-5
1.996E-3
1.160E-3
0
0
0.553
0.393
0.153
0
1.75E-03
6.02E-05
6.63E-03
Comparison Curves:
Effect of Process Parameters on Molecular Release: An Exhaustive Search
Fig depicts the two bottlenecks identified using the model: leak during the forward cycle and retention at the end of the reverse cycle for varying voltage scan rate. Before elaborating the results of the exploration of the dynamics of ‘controlled molecular
release system’, let us first define the base cases (good and bad) of molecular release.
Recent Developments:-Similar experiments are now conducted by
using SSA doped PANI, and the bright side in such experiments is that the PANI-SSA is experimentally synthesized.
The Synthesized PANI-SSA serves as a potentially better source of such experimentation.
It will be not long before a miniaturized version of the experimental setup becomes scientifically viable.
Acknowledgements: I would like to convey my gratitude to the Department Of Biotechnology (DBT-INDIA) for
financially assisting the work.
My regards for Prof. Kajari Kargupta and Dr. Saptarshi Majumdar for their valuable and
expert guidance, keen interest, fruitful suggestions and unwavering encouragement
during the entire period of project work.
Finally I would like to specially thank Mr. Ajay Prodhan, the lab assistant without whom the
work would never have been completed.
Achievements :
Morphological Studies (TEM) show a connected nano -particle like structure of the polymer membrane(<50 nm)
Prediction of release pattern
A protocol for different time scan and different release pattern is obtained for different experimentation
Drawbacks :
Mechanical leakage : Teflon – metal joints : modifications of design
Membrane stability crucially depends on the parameters of electro-deposition : leakage in membrane
Oxidation of the membrane due to exposure with the environment
Conclusions: