Development of optimally controlled drug release device using
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This document provides details of a project to develop a smart drug delivery device using an electro-active polymer membrane. The project is guided by Prof. Kajari Kargupta and Dr. Saptarshi Majumdar. The device aims to lower side effects, increase drug effectiveness and bioavailability by targeted drug release. Polyaniline is investigated as the electro-active polymer membrane material. Experiments are conducted to characterize the membrane morphology, study drug transport under electric fields, and control release patterns. The findings provide insights into optimizing the device design and electro-deposition parameters to achieve controlled molecular release.
Development of optimally controlled drug release device using
- 1. Project Guide: Prof. Kajari Kargupta Dept. Of Chemical Engineering Jadavpur University Dr. Saptarshi Majumdar Dept. Of Chemical Engineering Indian Institute Of Technology Hyderabad
- 2. Development of Smart Device : An electro-active Polymer based drug delivery device
- 3. 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
- 4. Commercial success can be found in following therapeutic categories: Asthma Pain Management Cardiovascular Disease Dermatological Women’s Health Medicines Applications Dexamethasone Neuro Inflammations Dopamine Neurotransmitter Sodium Salisylate Liver treatment ATP Stimulator
- 5. 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)
- 6. DIFFERENT OXIDATION STATES OF POLYANILINE Only emeraldine (salt) is conductive
- 7. 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 .
- 8. 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.
- 9. 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 :
- 10. Testronics Voltage Source Polymer membrane
- 11. Scanning Electron Micrograph (SEM) PANI(salt)-p-TSA 50 µm 100 µm
- 13. X-Ray Diffraction 0 10 20 30 40 50 60 70 0 100 200 300 400 500 Intensity(cps) 2 theta (degrees) 2d sin θ = n λ
- 14. Studies on transport of ionic drug through polymeric film under applied time varying electric field.
- 15. Voltage (Positive Scan) + + + - + - + - + - - - Voltage (Negative Scan) - - - I Porous Base CP Film: Modified Working Electrode Counter Electrode Permeate Side Feed Side
- 16. Schematic Diagram of Experimental setup for Drug Release Study DRUG RESERVOIR (A) MEMBRANE BODY FLUID (B) POROUSSILVER PLATE L1=10cm 4cm L2=5cm 2.5cm COMPUTE R RE SAMPLE WITHDRAWING A/D CONVER TER 4.290 OPENING SLOTWECE meshGas cade ONLINE pH and Conductivity measurement Porous Silver plate ID 2.5cm Offline UV-VIS Spectrophotometer
- 18. Platinum mesh (CE)Platinum mesh (CE) Polymer membrane(WE) Gold thread (RE)
- 19. 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
- 20. 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
- 21. 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 (i) OCP run: Study on diffusion characteristic with no applied voltage (ii) Release due to Step potential (iii) Release induced by Cyclic Voltammetry
- 22. Release pattern of para- toluene- sulfonic acid through Polyaniline (PANI) salt membrane in single compartment:
- 23. RESULT: 0 1000 2000 3000 4000 5000 0.00 0.02 0.04 0.06 0.08 0.10 Concentration(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 0.3μmole/s
- 24. 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
- 26. Details of experimentation for PTSA-PANI: Membrane i) 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) = 30V Duration=2hr Current Variation =0.08A Drug Delivery Cell data Duration 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: Membrane i) 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) = 30V Duration=2hr Current Variation =0.08A Drug Delivery Cell data Duration of experiment= 150min Open Circuit Potential: (for 600sec) Feed side: 0.1(M) SSA solution. Permeate side: Distilled Water.
- 28. 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-5 1 -0.242 0.05 0.004 2.93E-5 5.814E-6 2 -0.330 0.05 0.005 2.589E-4 6.6E-6 3 -0.283 0.1 0.005 2.102E-4 3.034E-6 5 -0.294 0.15 0.005 1.132E-4 4.34E-6
- 30. EFFECT ON FLUX AT DIFFERENT SCAN RATE Scan 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
- 32. 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.
- 33. 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.
- 34. 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.
- 35. 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