Seminar on Nanoparticles

1. PRESENTATION ON NANOPARTICLES DEPARTMENT OF FORMULATION R&D

4. Carriers Used for NDDS or TDD: Carriers for transportation and retain of the loaded drug(s). Colloidal carriers: Vesicular systems: Liposomes; pharmacosomes; virosomes; immunoliposomes. Micro particulate systems: Nanoparticles ; Microparticles; Magnetic Microspheres; Nanocapsules. Pramolecular delivery sys Cellular carriers: Resealed erythrocytes; Serum albumin; Antibodies; Platelets; Leukocytes. Supramolecular delivery system: Micelles; reverse micelles; mixed micelles; polymeric micelles; liquid crystal: lipoproteins. Polymer based systems: Signal sensitive; muco-adhesive; biodegradable; bioerodable; solute synthetic polymeric carriers.

5. Macromolecular carriers: Proteins, glycoproteins, neo glycoproteins and artificial viral envelops (AVE); Glycosylated water-soluble polymers (poly-L-lysine) Mabs; Immunological Fab fragments; antibody enzyme complex & bispesific Abs; Toxins, immunotoxin & rCD4 toxin conjugates Lecithins (Con A) & polysaccharides.

6. INTRODUCTION ABOUT NANOTECHNOLOGY: Nanotechnology is a broad interdisciplinary area of research, development and industrial activity. NANOPARTICLES: Nanoparticles are the end products of a wide variety of physical, chemical and biological processes some of which are novel and radically different, others of which are quite commonplace. Nanoparticles may be defined as submicron (<1µm) colloidal systems, generally, but not necessarily, made of polymers (biodegradable or not).

7. Thus, this term is some what general, since it does not take into account the morphology and structural organization of the system. According to the process used for the preparation of Nanoparticles, Nanospheres or Nanocapsules can be obtained. Nanocapsules are vesicular systems in which the drug is confined to a cavity surrounded by a unique polymeric membrane. Nanospheres are matrix systems in which the drug is dispersed throughout the particles.

13. Coacervation or Ionic Gelation Method: Much research has been focused on the preparation of nanoparticles using biodegradable hydrophilic polymers such as chitosan, gelatin and sodium alginate. Supercritical Fluid Technology: Supercritical Fluid Technology has been investigated as an alternative to prepare biodegradable micro and nanoparticles because supercritical fluids are environmentally safe. A supercritical fluid can be generally defined as a solvent at a temperature above its critical temperature, at which the fluid remains a single phase regardless of pressure. Supercritical CO 2 is the most widely used supercritical fluid because of its mild critical conditions, non-toxicity, non-flammability and low price.

15. ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) Currently Marketed Paclitaxel Nanoparticles: DESCRIPTION ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) is an albumin-bound form of paclitaxel with a mean particle size of approximately 130 nanometers. Paclitaxel exists in the particles in a non-crystalline, amorphous state. ABRAXANE is supplied as a white to yellow, sterile, lyophilized powder for reconstitution with 20mL of 0.9% Sodium Chloride Injection, USP prior to intravenous infusion. Each single-use vial contains 100 mg of paclitaxel and approximately 900 mg of human albumin. Each milliliter (mL) of reconstituted suspension contains 5 mg paclitaxel. ABRAXANE is free of solvents. ABRAXIS BIOSCIENCE Distributed by Abraxis Bioscience, LLC Bridgewater, NJ 08807

16. Preparation for Intravenous Administration: ABRAXANE is supplied as a sterile lyophilized powder for reconstitution before use. AVOID ERRORS, READ ENTIRE PREPARATION INSTRUCTIONS PRIOR TO RECONSTITUTION . 1. Aseptically, reconstitute each vial by injecting 20 mL of 0.9% Sodium Chloride Injection, USP. 2. Slowly inject the 20 mL of 0.9% Sodium Chloride Injection, USP, over a minimum of 1 minute, using the sterile syringe to direct the solution flow onto the INSIDE WALL OF THE VIAL. 3. DO NOT INJECT the 0.9% Sodium Chloride Injection, USP, directly onto the lyophilized cake as this will result in foaming. 4. Once the injection is complete, allow the vial to sit for a minimum of 5 minutes to ensure proper wetting of the lyophilized cake/powder. 5. Gently swirl and/or invert the vial slowly for at least 2 minutes until complete dissolution of any cake/powder occurs. Avoid generation of foam. 6. If foaming or clumping occurs, stand solution for at least 15 minutes until foam subsides.

17. Stability: Unopened vials of ABRAXANE are stable until the date indicated on the package when stored between 20ºC to 25ºC (68ºF to 77ºF), in the original package. Neither freezing nor refrigeration adversely affects the stability of the product. Stability of Reconstituted Suspension in the Vial: Reconstituted ABRAXANE should be used immediately, but may be refrigerated at 2ºC to 8ºC (36ºF to 46ºF) for a maximum of 8 hours if necessary. If not used immediately, each vial of reconstituted suspension should be replaced in the original carton to protect it from bright light. Discard any unused portion. Stability of Reconstituted Suspension in the Infusion Bag: The suspension for infusion prepared as recommended in an infusion bag should be used immediately, but may be stored at ambient temperature (approximately 25º C) and lighting conditions for up to 8 hours.

18. Drug Profile: Drug Name: Paclitaxel Molecular Formula: C 47 H 51 NO 14 Synonym:Taxol Molecular weight:853.906g/mol Melting point:214.5°C BCS classification: Class IV (Low permeability and Low solubility) Storage: store at 2°C-8°C Solubility: Insoluble in cold and hot water. Bioavailability: 6.5% Protein binding: 89 to 98% Clinical use: Used for Ovarian, breast and lung cancers and also used to treat AIDS related Kaposi’s Sarcoma

19. Polymer Profile: Name: Human Serum Albumin 25% solution Solubility: Soluble in water Storage: Store BUMINATE 25% at room temperature, not to exceed 30°C (86°F). Avoid freezing to prevent damage to the bottle.

20. Method of Preparation of Paclitaxel Nanoparticles: HSA 25% Solution + Chloroform + Paclitaxel (solid form) Formation of Mixture By using Mechanical Stirrer or Magnetic Stirrer In process checks : RPM, Time Formation of Emulsion containing Nanoparticles By using High Shear Mixture In process checks : RPM, Time Formation of Nanoemulsion By using Homogenizer In process checks : Pressure, Cycles (Continuous next slide)

21. Formation of Solvent Free Nanoemulsion By using Rotary Vacuum Evaporator evaporate chloroform In process checks : RPM, Time & Temperature. Filtered Nanoemulsion By using 0.2µm membrane filter, filter Nanoemulsion Formation of Lyophilized cake Lyophilize the Nanoemulsion by using Lyophilizer In process checks : Time (hrs), Vacuum Pressure.