Polymeric nanoparticles A Novel Approach

8,412 views

Published on

Extensively guided by my ma'm cum Idol Ms Rudree Pathak

Published in: Education, Technology, Business
0 Comments
15 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
8,412
On SlideShare
0
From Embeds
0
Number of Embeds
4
Actions
Shares
0
Downloads
953
Comments
0
Likes
15
Embeds 0
No embeds

No notes for slide

Polymeric nanoparticles A Novel Approach

  1. 1. Prepared by: Shivam Thakore Guided by: Ms Rudree Pathak Ankit Patel 7/26/2013 1 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad
  2. 2. Table of Contents  Introduction  Advantages  Disadvantages  Polymers used  Method Of Preparation  Characterization  Questions that can be asked  References 7/26/2013 2 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad
  3. 3. Introduction: Polymeric Nanoparticles • What are PNP’s? ○ They are solid colloidal particles ranging in size from 10 to 1000 nm (1µm).  Drug may be dissolved, entrapped, encapsulated or attached to a nanoparticle matrix .  Because these systems have very high surface areas, drugs may also be adsorbed on their surface.  Polymer-based nanoparticles effectively carry drugs, proteins and DNA to target cells and organs.  Their nanometer-size promotes effective permeation through cell membranes and stability in the blood stream 7/26/2013 3 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad
  4. 4. Depending upon Method of Preparation Nanospheres Nanocapsules 7/26/2013 4 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad
  5. 5. 7/26/2013 5 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad
  6. 6.  Nanocapsules: They are the systems in which the drug is confined to a cavity surrounded by a unique polymer membrane.  Nanospheres: They are the matrix systems in which the drug is physically and uniformly dispersed. 7/26/2013 6 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad
  7. 7. Advantages  Increases the stability of any volatile agents & can be easily and cheaply fabricated in large quantities by a multimethods.  Has significant advantages over traditional oral and intravenous methods of administration in terms of efficiency and effectiveness.  Delivers a higher concentration of pharmaceutical agent.  The choice of polymer and the ability to modify drug release from polymeric nanoparticles have made them ideal candidates for cancer therapy, delivery of vaccines, contraceptives and delivery of targeted antibiotics. 7/26/2013 7 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad
  8. 8. Cont…  Targeted Drug Delivery System.  Polymeric nanoparticles can be easily incorporated into other activities related to drug delivery, such as tissue engineering  Other all advantages over single unit dosage forms are as such 7/26/2013 8 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad
  9. 9. Disadvantages  Very costly formulation with no low yield  Productivity is more difficult. As a industrial applications, Technology transfer to commercial production is very difficult.  Reduced ability to adjust the dose  Highly sophisticated technology  Requires skills to manufacture.  Stability of dosage form is big issue owing to its nano size. 7/26/2013 9 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad
  10. 10. Polymers used in Preparation Natural Hydrophilic Proteins Polysaccharides Synthetic Hydrophobic Pre-Polymerized Polymerized in process 7/26/2013 10 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad
  11. 11. PROTIENS POLYSACHCHARIDES Gelatin Alginate Albumin Dextran Lectin Chitosan Legumine Agarose Viciline Pullulan PRE-POLYMERIZED POLYMERIZED IN PROCESS Poly E caprolactone Poly Isobutyrl cyano acrylates (PICA PLA PBCA Poly lactide co glycolide (PLGA) PHCA Polystyrene Poly methyl methacyrlate (PMMA) 7/26/2013 11 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad
  12. 12. Method of Preparation 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 12 Polymerization based methods Polymer precipitation methods Amphiphilic macromolecul e cross-linking
  13. 13. 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 13 Heat Cross- linking Chemical Cross- linking Amphiphilic macromolecule cross-linking
  14. 14. 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 14 Polymerization based Methods Polymerization of monomers Emulsion polymeriza tion Interfacial complexat ion Dispersion polymerization Interfacial condensation polymerization
  15. 15. 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 15 Polymer Precipitation methods Solvent extraction/ evaporation Solvent displacement (nanoprecipitation) Salting out
  16. 16. 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 16
  17. 17. Heat / Chemical Cross-Linking 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 17 Aq protein (BSA), Surfactant Oil High Pressure Homoginization W/O emulsion Centrifugation & isolation of nanoparticles Dilution with preheated oil {Heat CL} or Add cross-linking agent {chemical CL}
  18. 18. 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 18
  19. 19. Solvent extraction method(SEM) Single emulsion 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 19 Organic phase, Solvent, Drug, Polymer Aqueous phase, Distille d water, stabiliz er Sonication, homo genizaion O/W emulsion Oil droplet Solvent evaporation Nano particles obtained
  20. 20. Double Emulsion SEM 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 20 Organic phase, solvent, drug, polymer Aqueous Phase, Water, Stabilizer Sonication, homo genization W/O emulsion stablized at 4 C W/O/W emulsion Nano particles Aq phase with stabilizer(PVA) Solvent evaporation
  21. 21. Solvent Displacement (Nanoprecipitation) 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 21 Aq phase Distilled water, Poloxamer 188 Organic phase, Organic solvent, Polymer, drug Nano spheres Aq phase Distilled Water, Poloxa mer 188 Organic phase, Polar solvent, Oil, Polymer, Drug Nano capsules Magnetic stirring
  22. 22. Salting Out 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 22 Org phase. Org solvent, Drug, Polymer Aq phase, dist water, PVA, MgCl2 Mechanical Stirring O/W emulsion Nano spheres Dist Water
  23. 23. 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 23
  24. 24. Emulsion Polymerization  It may be conventional or reverse, depending upon nature of continuous phase,  Conventional method= Aq phase in Continuous  Reverse method= Organic is continuous phase 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 24 Monomer is emulsified in non-solvent partially soluble phase with stabilizer, leading to formation of monomer swollen micelles
  25. 25. 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 25 Polymerization takes place in presence of intiator (chemical/physical), which provides energy to monomer, So that in becomes Free Reactive radical It collides with the surrounding unnreactive monomers, and initiates the POLYMERIZATiON reaction. It continues till concentration of monomer/intiator is consumed Mechanism is micellar polymerization were Swollen monomer micelles act as a site of nucleation & polymerization
  26. 26. 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 26 As monomer is slightly soluble in surrounding phase, it diffuses from monomer droplets and reach monomer micelles through continuous phase. Thus polymerization takes places in MICELLES.
  27. 27. Be careful while using Chemical initiator 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 27 Flush the Aq medium with nitrogen gas for 1hr to remove completely oxygen from it. Interferes the radical polymerization process, Apart from that it forms O radical & We already know HOW HARMFUL THEY ARE!!!! Ammonium or Potassium Peroxodisulfate
  28. 28. Dispersion polymerization 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 28 Here, monomer instead of being dispersed, is dissolved in the Aq medium, which act as a precipitant for formed polymer. Nucleation is directly induced in Aq. Monomer solution. So STABILIZER/ SURFACTANT is no needed Initiation here is achieved by different mechanism, but mostly it is by irradiating solution with high energy radiation (g, UV, strong visible light). PROCESS GOES AS EMULSION POLYMERIZATION
  29. 29. Interfacial condensation Polymerization 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 29 It involves step polymerization of two different monomers, dissolved in two phases respectively, Continuous and Dispersed phase. Polymerization reaction takes place at the interfaces of two liquids. Nanometre-sized hollow polymer particles were synthesized by employing interfacial cross-linking reactions as polyaddition and polycondensation or radical polymerization.
  30. 30. 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 30 Oil-containing nanocapsules were obtained by the polymerization of monomers at the oil/water interface of a very fine oil-in-water micro- emulsion. The organic solvent, which was completely miscible with water, served as a monomer vehicle and the interfacial polymerization of the monomer was believed to occur at the surface of the oil droplets that formed during emulsification Reverse is the case with preparation of water containing Nanocapusles
  31. 31. Characterization of PNP’s  Particle size and size distribution  Surface area, surface chemistry, surface coating and porosity  Hydrophilicity and surface charge density  Purity and quality  Stability (on shelf and upon administration)  Drug release parameters and bioequivalence testing considerations  % Entrapment efficiency  % PNP Yield 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 31
  32. 32. Size evaluation  Done by number of methods with/without Freeze fracture like  Photon correlation spectroscopy,  Transmission electron microscopy(TEM)  Scanning electron microscopy(SEM)  The spherical shape of the nanocapsules was confirmed by atomic force microscopy  At present, TEM is most successfully used in determining the nanocap structure, polymer envelope and the inner cavity & allowing the wall thickness to be estimated. 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 32
  33. 33.  Laser Difractometry : For larger particles  Freeze fracture has also allowed the visualization of different possible organizations of lipophilic surfactant, which can form vesicles, micelles, Bilayers, Monolayers, 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 33
  34. 34. Surface Charge, Molecular Wt, Structure & Crystallinility  Surface Charge: Measuring particle velocity in electric field  Molecule charge: Gel permeation  For Structure/crystallinity different thermal methods are used  DSC  DTA  TGA 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 34
  35. 35. Purity, % EE, % Yield  Purity & Quality: Assay of PNP with suitable estimation techniques.  % Entrapement Efficency:  % Yield: 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 35
  36. 36. In vitro Drug release  Ideally Franz-diffusion cell is used, but is not appropriate for nano/multiparticulate DDS.  Hence, generally, Cellophane bag filled with the product is used, that is dipped suitable in the beaker filled with proper media, aliquots are taken at regular time intervals. 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 36
  37. 37. Applications in some areas of medicine  Corticoids release  Anticancer therapy  Crossing BBB  Vaccines and gene therapy  Diagnostic  Ocular delivery 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 37
  38. 38. 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 38
  39. 39. Products in Pipeline Company Technology API Route of administration Novavax, USA Micellar nanoparticles Testosterone S.c. BioAUiance, France Polydsohexyl cyanoacrylate) nanoparticles Doxorubicin i.v. American Bioscience, USA Albumin-Drug nanoparticles Paclitaxel i.v. Wyeth Pharmaceutical, USA Drug Nanoparticles Rapamycin Oral BioSante, USA Calcium phospahte nanoparticles Insulin Oral 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 39
  40. 40. Question to Crack GTU  Define nanotechnology and various products prepared by it. Explain application of nanoparticles and nanosuspensions giving examples for their market products. 5M JAN 2011  Briefly introduce the term nanotechnology. Enlist the commonly used polymers into these products. Discuss any one method of preparation of nanoparticle. 6M JUNE 2011  Write about applications of nanoparticulate drug delivery system. 5M JUNE 2011 7/26/2013 40 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad
  41. 41.  Explain the terms Nanotechnology and Nanoparticles. Enumerate different parameters and characterization methods for each parameter in context to characterization of Nanoparticulate system. 8M MAY 2012  Nanotechnology and its applications 5M NOV 2012  Give application of nanotechnology in the field of pharmaceutical science 5M DEC 2011 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 41
  42. 42. References  Kumari A, Yadav S, Yadav SC, “Biodegradable polymeric nanoparticles based drug delivery systems”,Colloids and Surfaces B: Biointerfaces , elsevier.com, 2010, vol 75 Pg:1–18  Nagavarma BVN, Yadav HKS*, Ayaz A, Vasudha LS, Shivakumar HG. “Different techniques for preparation of polymeric nanoparticles- a review ”, Asian J Pharm Clin Res, Vol 5, Suppl 3, 2012, Pg.16-23  Jain N.K. “Advances in controlled and novel Drug Delivery”, CBS publisher & Distributers, Edition 1st 2001, Pg. 408 7/26/2013 42 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad
  43. 43.  Zhang G, Niu A, Peng S, Jiang M, Tu Y, Li M, Wu C, “Formation of Novel Polymeric Nanoparticles”, vol. 34, no. 3, 2001 / accounts of chemical research, pg .249- 256  Kreuter J, “Nanoparticles—a historical perspective”, International Journal of Pharmaceutics, vol 331 (2007) elsevier.com,Pg. 1–10  Cismaru L, Popa M,” polymeric nanoparticles with biomedical applications”, Rev. Roum. Chim., vol 55(8) 2010, Pg 433-442 7/26/2013 43 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad
  44. 44.  Khar RK and Vyas SP, “Targetted and controlledd drug delivery”  Torchilin p v, “nanoparticulates drug carriers”, imperial college press, london 7/26/2013 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad 44
  45. 45. 7/26/2013 45 Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad

×