Nanopowder Production and Characteristics

1. Nanopowder Production and Characteristics Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D Department of Pharmaceutics KLE University College of Pharmacy BELGAUM-590010 Cell No: 0091-9742431000 E-mail: nanjwadebk@gmail.com FDP on Nanotechnology, VTU, Belgaum.

2. Nanotechnology FDP on Nanotechnology, VTU, Belgaum.

3. Nanotechnology • Nanotechnology may be defined as the ability to work at the molecular level, atom by atom, to create large structure with fundamentally new molecular organization. • Many pharmaceutical companies are performing research to decline the particle size. • If drugs were able to have smaller particle size they would be better absorbed by digestive tract lining therefore the amount necessary would be reduced making medicines more affordable. FDP on Nanotechnology, VTU, Belgaum.

4. Manufacturing Methods • Several mechanically or chemically based methods are currently in use to manufacture nanomaterials. • Major mechanical methods include ball milling, laser ablation, etching, sputtering, sonification and electroexplosion. • Major chemical methods include chemical vapor deposition (CVD), sol-gel processing and molecular pyrolysis. FDP on Nanotechnology, VTU, Belgaum.

5. What is a Nanopowder • Nanopowder is a material fabricated on the nanoscale with grain and feature sizes typically under 100 nanometres. • The basis of nanotechnology is the ability to form nano-sized particles, for example nanopowders, which are solid particles that measure on the nanoscale. • Nanopowders have been of extreme interest in the pharmaceutical field. • Drug delivery has been impacted in several ways due to the advances in nanopowder technology. FDP on Nanotechnology, VTU, Belgaum.

6. Production of Nanopowder • Conventional Methods - Milling, grinding, jet milling, crushing, and air micronization • Super Critical Fluids (SCF) • Rapid Expansion of Supercritical Solutions (RESS) • Supercritical Anti-Solvent (SAS) • Aerosol Solvent Extraction System (ASES) • Solution Enhanced Dispersion by Supercritical fluids (SEDS) • Particles from Gas Saturated Solutions (PGSS) • Depressurization of Expanded Liquid Organic Solution (DELOS) FDP on Nanotechnology, VTU, Belgaum.

7. Conventional Methods • Conventional methods of particle size reduction include milling, grinding, jet milling, crushing, and air micronization. • CM might not accomplish the desired amount of particle size reduction. • CM drawback is associated with the physical and chemical properties of the materials undergoing size reduction. • Certain compounds are chemically sensitive or thermo-liable, such as explosives, chemical intermediates, or pharmaceuticals which can not be processed using conventional methods due to the physical effects of these methods. FDP on Nanotechnology, VTU, Belgaum.

8. Super Critical Fluid • A SCF is defined as a substance above its critical temperature (T) and critical pressure (P). • The critical point represents the highest temperature and pressure at which the substance can exist as a vapor and liquid in equilibrium. FDP on Nanotechnology, VTU, Belgaum.

9. Rapid Expansion of Supercritical Solutions (RESS) • Rapid Expansion of Supercritical Solutions (RESS) is a crystallization technique that uses the properties of a supercritical fluid, typically CO2, as a solvent to facilitate nanopowder production. • The RESS process is described in two steps: solubilization and particle formation. • The driving force for this process is caused by the rapid depressurization of the supercritical fluid dissolved with the solute of interest through a nozzle to cause fast nucleation and fine particle generation FDP on Nanotechnology, VTU, Belgaum.

10. Schematic of RESS Process FDP on Nanotechnology, VTU, Belgaum.

11. Supercritical Anti-Solvent • The Supercritical Anti-Solvent process (SAS) uses solvent/anti-solvent binary systems to induce the formation of nano and micro-size particles. • The supercritical fluid (i.e. CO2) acts as an anti-solvent that causes the crystallization of the solute. • The main driving force for this process is the droplet formation, which is caused by the solvent/anti-solvent interaction. FDP on Nanotechnology, VTU, Belgaum.

12. Schematic of SAS Process FDP on Nanotechnology, VTU, Belgaum.

13. Aerosol Solvent Extraction System (ASES) • ASES method involves spraying the solution as fine droplets into the supercritical fluid. • The dissolution of the supercritical fluid is followed by a large volume expansion, which is called the anti-solvent effect. • This cause a reduction in the liquid solvating power and a sharp increase in the supersaturated within the liquid mixture, which leads to small and uniform particles FDP on Nanotechnology, VTU, Belgaum.

14. Schematic of ASES Process FDP on Nanotechnology, VTU, Belgaum.

15. Solution Enhanced Dispersion System(SEDS) • SEDS method was developed to achieve smaller droplet size and intense mixing of supercritical fluid and solution for increased mass transfer rates. • The supercritical fluid is used for its chemical properties and as a ‘spray enhancer’ by mechanical effects. FDP on Nanotechnology, VTU, Belgaum.

16. Schematic of SEDS Process FDP on Nanotechnology, VTU, Belgaum.

17. Particle From gas Saturated Solution (PGSS) • The Particle from Gas Saturated Solution (PGSS) process uses a SCF, usually CO2, as a solute to crystallize a solution. • The PGSS process can be used to create micro and nano sized particles with the ability to control particle size distribution. • The driving force of the PGSS is a sudden temperature drop of the solution below the melting point of the solvent. FDP on Nanotechnology, VTU, Belgaum.

18. Particle From gas Saturated Solution (PGSS) • This occurs as the solution is expanded from a working pressure to atmospheric conditions due to the Joule-Thompson effect. • The rapid cooling produces amorphous powder which is mainly used in pharmaceutical industries. FDP on Nanotechnology, VTU, Belgaum.

19. Schematic of PGSS Process FDP on Nanotechnology, VTU, Belgaum.

20. Depressurization of an Expanded Liquid Organic Solution (DELOS) • Depressurization of an expanded liquid organic solution (DELOS) is a process that uses a supercritical fluid, as a co-solvent for the formation of micro and nano- sized particles. • DELOS process is best for organic solutes in organic solvents and it is particularly useful for pharmaceuticals, dyes, and polymers, where conventional methods of particle size reduction tend to be ineffective due to physical and chemical limitations FDP on Nanotechnology, VTU, Belgaum.

21. Schematic of DELOS Process FDP on Nanotechnology, VTU, Belgaum.

22. Applications of Nanopowders • Nanopowder has many applications in different fields • Ceramics used in nano sized powders are more ductile at elevated temperatures compared to coarse grained ceramics and can be sintered at low temperatures • Nano sized powders of iron and copper have hardness about 4-6 times higher than the bulk materials because bulk materials have dislocations. • Nano sized copper and silver are used in conducting ink and polymers FDP on Nanotechnology, VTU, Belgaum.

23. Applications of Nanopowders • Nano powder has various applications in the pharmaceutical and medical field. • Drug delivery has impacted by the advancement in nano powders smaller particles are able to be delivered in new ways to patients, through solutions, oral or injected, and aerosol, inhaler or respirator. • New production processes allow for encapsulation of pharmaceuticals which allow for drug delivery where needed with in the body. FDP on Nanotechnology, VTU, Belgaum.

24. Nanopowder Characteristics 1. Morphology 2. Surface 3. Chemical 4. Other FDP on Nanotechnology, VTU, Belgaum.

25. 1. MORPHOLOGY i. Size (Primary particle) ii. Size (Primary/aggregate/agglomerate) iii. Size distribution iv. Molecular weight v. Structure/Shape vi. Structure/Shape(3D structure) FDP on Nanotechnology, VTU, Belgaum.

26. i. Size (Primary particle) a. TEM – Transmission electron microscopy b. SEM – Scanning electron microscopy c. AFM – Atomic absorption spectroscopy d. XRD – X-ray diffraction FDP on Nanotechnology, VTU, Belgaum.

27. ii. Size (primary/aggregate/agglomerate) a. TEM – Transmission electron microscopy b. SEM – Scanning electron microscopy c. AFM – Atomic force microscopy d. DLS – Dynamic light scattering e. FFF – Field flow fractionation f. AUC – Analytical ultracentrifugation g. CHDF – Capillary hydrodynamic fractionation h. XDC – X-ray disk centrifuge i. HPLC – High performance liquid chromatography j. DMA(1) – Differential mobility analyzer FDP on Nanotechnology, VTU, Belgaum.

28. iii. Size distribution a. TEM – Transmission electron microscopy b. SEM – Scanning electron microscopy c. AFM – Atomic force microscopy d. DLS – Dynamic light scattering e. AUC – Analytical ultracentrifugation f. FFF – Field flow fractionation g. HPLC – High performance liquid chromatography h. SMA – Scanning mobility particle sizer FDP on Nanotechnology, VTU, Belgaum.

29. iv. Molecular weight a. SLS – Static light scattering b. AUC – Analytical ultracentrifugation c. GPC – Gel permeation chromatography FDP on Nanotechnology, VTU, Belgaum.

30. v. Structure Shape a. TEM – Transmission electron microscopy b. SEM – Scanning electron microscopy c. AFM – Atomic force microscopy d. NMR – Nuclear magnetic resonance FDP on Nanotechnology, VTU, Belgaum.

31. vi. Stability (3D structure) a. DLS – Dynamic light scattering b. AUC – Analytical ultracentrifugation c. FFF – Field flow fractionation d. SEM – Scanning electron microscopy e. TEM – Transmission electron microscopy FDP on Nanotechnology, VTU, Belgaum.

32. 2. SURFACE • Surface area • Surface charge • Zeta potential • Surface coating composition • Surface coating coverage • Surface reactivity • Surface-core interaction • Topology FDP on Nanotechnology, VTU, Belgaum.

33. i. Surface area a. BET – Brunauer, Emmett, and Teller method FDP on Nanotechnology, VTU, Belgaum.

34. ii. Surface charge a. SPM – Surface probe microscopy (AFM, STM, NSOM/SNOM, etc) b. GE – Gel electrophoresis c. Titration methods - FDP on Nanotechnology, VTU, Belgaum.

35. iii. Zeta potential a. LDE – Laser doppler electrophoresis b. ESA – Electroacoustic spectroscopy c. PALS – Phase analysis light scattering FDP on Nanotechnology, VTU, Belgaum.

36. iv. Surface coating composition a. SPM – Surface probe microscopy (AFM, STM, NSOM/SNOM, etc.) b. XPS – X-ray disk centrifuge c. MS – Mass spectrometry (GCMS, TOFMS, SIMS, etc.) d. RS – Raman spectroscopy e. FTIR – Fourier transform infrared spectroscopy f. NMR – Nuclear magnetic resonance FDP on Nanotechnology, VTU, Belgaum.

37. v. Surface coating coverage a. AFM – Atomic force microscopy b. AUC – Analytical ultracentrifugation c. TGA – Thermal gravimetric analysis FDP on Nanotechnology, VTU, Belgaum.

38. vi. Surface reactivity a. Varies with nanomaterial FDP on Nanotechnology, VTU, Belgaum.

39. vii. Surface-core interaction a. SPM – Surface probe microscopy (AFM, STM, NSOM, etc. ) b. RS – Raman spectroscopy c. ITC – Isothermal titration calorimetry d. AUC – Analytical ultracentrifugation e. GE – Gel electrophoresis FDP on Nanotechnology, VTU, Belgaum.

40. viii. Topology a. SEM – Scanning electron microscopy b. SPM – Surface probe microscopy (AFM, STM, NSOM/SNOM, etc.) c. MS – Mass spectrometry (GCMS, TOFMS, SIMS, etc.) FDP on Nanotechnology, VTU, Belgaum.

41. 3. CHEMICAL • Chemical composition (core, surface) • Purity • Stability (chemical) • Solubility (chemical) • Structure (chemical) • Crystallinity • Catalytical activity FDP on Nanotechnology, VTU, Belgaum.

42. i. Chemical composition (core, surface) a. XPS – X-ray photoelectron spectroscopy b. MS – Mass spectrometry (GCMS, TOFMS, SIMS, etc.) c. AAS – Atomic absorption spectroscopy d. ICP-MS – Inductively coupled plasma mass spectrometry e. RS – Raman spectroscopy f. FTIR – Fourier transform infrared spectroscopy g. NMR – Nuclear magnetic resonance FDP on Nanotechnology, VTU, Belgaum.

43. ii. Purity • ICP-MS - Inductively coupled plasma mass spectrometry • AAS – Atomic absorption spectroscopy • AUC – Analytical ultracentrifugation • HPLC – High performance liquid chromatography • DSC – Differential scanning calorimetry FDP on Nanotechnology, VTU, Belgaum.

44. iii. Stability (chemical) • MS – Mass spectrometry (GCMS, TOFMS, SIMS, etc.) • HPLC – High performance liquid chromatography • RS – Raman spectroscopy • FTIR – Fourier transform infrared spectoscopy FDP on Nanotechnology, VTU, Belgaum.

45. iv. Solubility (chemical) a. Varies with nanomaterial FDP on Nanotechnology, VTU, Belgaum.

46. v. Structure (chemical) • NMR – Nuclear magnetic resonance • XRD – X-ray diffraction FDP on Nanotechnology, VTU, Belgaum.

47. vi. Crystallinity • XRD - X-ray diffraction • DSC – Differential scanning calorimetry FDP on Nanotechnology, VTU, Belgaum.

48. viii. Catalytic activity • Varies with nanomaterial FDP on Nanotechnology, VTU, Belgaum.

49. 4. OTHER • Drug loading • Drug potency/functionality • In vitro release (detection) • Deformability FDP on Nanotechnology, VTU, Belgaum.

50. i. Drug loading • MS – mass spectrometry (GCMS, TOFMS, SIMS, etc.) • HPLC – High performance liquid chromatography • UV-Vis – Ultraviolet-visible spectrometry • Varies with nanomaterial FDP on Nanotechnology, VTU, Belgaum.