size redn.pptx Facilitate Absorption & Bioavailability: - Rate of absorption depends on particle size. Finer the particles faster the rate of absorption

Improve Appearance: -
Smooth texture and elegant appearance (Ointments, Pastes and Creams).
Improve physical stability. Increase Surface Area: -
o Increase Dissolution
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Rate of absorption depends on particle size.
Finer the particles faster the rate of absorption
Facilitate Absorption & Bioavailability: -
Facilita

1. Size Reduction Ms. Neha Arora Associate Professor School of Pharmacy ( SGVU) PHARMACEUTICAL ENGINEERING

2. Objectives To study about the – What is size reduction? Why we do size reduction? Factors affecting size reduction Mechanism of size reduction Methods of size reduction Theories of size reduction 21-06-2024 Unit No.: 1.2; Lecture No.: 2

3. Learning Outcomes Students will learn about the : Size reduction process and why we do size reduction? Factors that affect size reduction process Mechanism, methods and theories of size reduction. 21-06-2024 Unit No.: 1.2; Lecture No.: 3

4. Size Reduction Physical Dimension of an object 4 Decrement or Decrease So, Size Reduction means decreasing size of an object 21-06-2024 Unit No.: 1.2; Lecture No.: 4

5. It is a unit operation in which materials are reduced to smaller pieces/ to coarse particles, or to still finer powder, before they can be formulated into suitable dosage forms. Other terms: - Co mm i n u t i o n Grinding Milling Pulverizing Crushing DEFINITION 5 21-06-2024 Unit No.: 1.2; Lecture No.: 5

6. Materials are rarely found in the size range required. So, there i s a need either t o d e cr e ase or to incre a se the particle size. Why Size reduction ?????????? 6 21-06-2024 Unit No.: 1.2; Lecture No.: 6

7. 1. Improve Appearance : - S m o o th t e xture a n d el e ga n t app e a r a nce (Oint m ent s , Pastes and Creams). Improve physical stability. 2. Increase Surface Area : - o Increase Dissolution rate  Increase therapeutic e f fi c i e ncy ( Gri s eo f ul v i n – fr e qu e n c y o f a dm inistra t i o n decrease). 3. Facilitate Absorption & Bioavailability : - Rate of absorption depends on particle size. Finer the part i c l es fa s t er the ra t e o f a bso r ption OBJECTIVES 7 21-06-2024 Unit No.: 1.2; Lecture No.: 7

8. 4. Improve Stability : - Sp. for biphasic systems – Suspension, Emulsion etc. Emulsion –  Size of oil droplets  Rate of creaming  Suspension –  rate of sedimentation 5. Extraction : - o More surface expose to solvent hence more extraction of drug ( Yavkuta in kwatha formation). 6. Mixing : - Easy mixing Assure uniform dosage 8 21-06-2024 Unit No.: 1.2; Lecture No.: 8

9. 7. Aerosol and Inhalation preparations : - o Size determines the position and retention of particles in bronchioles & less irritation. 8. Parenteral Suspension : - Rheology Product Syringeability 9. Facilitate drying : - Drying of wet masses may be facilitated by milling. Milling  surface area – Drying  . 9 21-06-2024 Unit No.: 1.2; Lecture No.: 9

10. 10. Ophthalmic suspension : - o Very fine to avoid eye-irritation. 11. To Increase Viscosity : - o Viscosity of Acacia increases on fine sub-division. Chemical reactivity 10 21-06-2024 Unit No.: 1.2; Lecture No.: 10

11. ADVANTAGES & DISADVANTAGES 11 21-06-2024 Unit No.: 1.2; Lecture No.: 11

12. AFFECTING FACTORS Size Redu c tion 12 Degree of Size Reduction 21-06-2024 Unit No.: 1.2; Lecture No.: 12

13. FACTORS AFFECTING SIZE REDUCTION 13 1. Hardness : - o Harder the material difficult is the size reduction. 2. Toughness : - Ex. Fibrous drugs, Green fresh leaves etc. are soft but tough. Toughness can be reduced by lowering the temperature. The advantages of this method are: Less decomposition of thermolabile material No loss of volatile material No oxidation No explosion 21-06-2024 Unit No.: 1.2; Lecture No.: 13

14. 3. Stickiness : - Cause difficulty in size reduction. Mat e ri a l may s t i c k t o the surf a ce o r m e s h m ay get choked. Solution: Dryness Addition of inert materials such as Kaolin to sulphur Ex. Gums & Resinous materials ( Guggulu , Mochras etc.) 4. Slipperiness : - o As material acts as lubricant. 14 21-06-2024 Unit No.: 1.2; Lecture No.: 14

15. 5. Moisture content : - Influ e nces prope r t i es such a s H a r dne s s, T ou g hne s s & Stickiness. Less than 5 % moisture – Dry grinding. More than 50 % - Wet grinding. 6. Melting or Softening point : - o Heat generated during grinding creates problems with materials which tend to melt/ stick/ decompose due to heat. 15 o Ex . Ca m pho r , T h ymol, Ste a ric a c ids, W axes, Fat s , Resins etc. 21-06-2024 Unit No.: 1.2; Lecture No.: 15

16. 7. Material Structure 8. Abrasiveness : - o If m a t er i al is abrasive the final powder with t he m e t al w o r n out m ay be from the c o nta m inat e d machine. Size of the starting material Quantity of material to be reduced Size, Shape, Flow & Bulk density of the product 12. Ratio of feed size to product size 16 21-06-2024 Unit No.: 1.2; Lecture No.: 16

17. MECHANISM OF SIZE REDUCTION Consists of two parts: - Fi r st o p e n ing up of any s m all fissu r es (cra c ks) which are already present. Secondly formation of new surfaces. L a r ge p articles with several cra c ks – Mo r e rapid size reduction. Small particles with less no. of cracks – Slow size reduction. Ex. Coal contains no. of small cracks – Large particles are broken more rapidly than the small ones. 17 21-06-2024 Unit No.: 1.2; Lecture No.:

18. Fine grinding needs more energy to initiate cracks. So, from Energy utilization point of view – Size reduction is an inefficient process. Efficiency of the process depends on: - Load applied Magnitude Nature of force exerted 18 21-06-2024 Unit No.: 1.2; Lecture No.:

19. m ain m e t h o ds e f fecting s i ze There a r e f o ur reduction: - 1. Cutting Compression Impact Attrition Impact and Attrition METHODS OF SIZE REDUCTION 19 21-06-2024 Unit No.: 1.2; Lecture No.:

20. 1. Cutting (Slicing): - The material is cut into pieces. It m ay b e e f fe c ted by a sha r p pen k n if e , a pair of scissors, or a root cutter. Equipment: - Cutter mill 2. Compression (Bruising): - Material is crushed by application of a pressure. Particle disintegration by two rigid forces. Equi p m en t : - Mortar and Pestle ( L a b o rato r y) and Roller mill (Industry) 20 21-06-2024 Unit No.: 1.2; Lecture No.:

21. 3. Impact: - The material is stationary and is hit by an object moving at high speed or Moving particles strikes a stationary surface. Size reduction occurs by a single rigid force. Equip m en t : - Mortar a n d Pest le (L a boratory) a n d H a m m er mill & Disintegrator (Industry) 4. Attrition: - Arising fr o m parti c les scrap i ng ag a inst one an o ther or against a rigid surface. Here, the material is subjected to pressure as in compression, but the surfaces are moving relative to each other. Equipment: - Roller mill 21 21-06-2024 Unit No.: 1.2; Lecture No.:

22. 5. Impact and Attrition: - Here, both impact and attrition are combined. Equipment: - Ball mill and Fluid energy mill 22 21-06-2024 Unit No.: 1.2; Lecture No.:

23. Me t h od Common example Approx. particle size (  m) 23 Approx. increase in fineness of the product C u tting Scissors Shears Guillotine Cutter mill 100 – 80,000 Com p r ession Pestle – Mortar Nutcrackers Roller mill 50 – 10,000 Im p act Hammer mill Disintegrator 50 – 8,000 Attrition Pestle – Mortar File Roller mill Colloidal mill 1 – 50 Impact & attrition Ball mill Fluid-energy mill 1 – 2000 21-06-2024 Unit No.: 1.2; Lecture No.:

24. THEORIES OF SIZE REDUCTION / MILLING A number of theories have been proposed to establish a relationship between energy input and the degree of size reduction produced. Rittinger’s theory Bond’s theory Kick’s theory Walker’s theory 21-06-2024 Unit No.: 1.2; Lecture No.: 24

25. Rittinger’s theory Rittinger’s theory suggests that energy required in a size reduction process is proportional to the new surface area produced. E= Kr (Sn-Si) where, E = energy required for size reduction Kr = Rittinger’s constant Si = initial specific surface area Sn = final specific surface area Application: It is most applicable in size reducing brittle materials undergoing fine milling. 21-06-2024 Unit No.: 1.2; Lecture No.: 25

26. Bond’s theory Bond’s theory states that the energy required for size reduction is inversely proportional to the square root of the diameter of the product. where, E = energy required for size reduction KB = Bond’s workindex di = initial diameter of particles dn = final diameter of particles Application: This law is useful in rough mill sizing. The work index is useful in comparing the efficiency of milling operations 21-06-2024 Unit No.: 1.2; Lecture No.: 26

27. Kick’s theory Kick’s theory states that the energy used in deforming (or fracturing) a set of particles of equivalent shape is proportional to the ratio of change of size/diameter where, E = energy required for size reduction KK = Kick’s constant di = initial diameter of particles dn = final diameter of particles Application: For crushing of large particles Kick’s theory most useful. 21-06-2024 Unit No.: 1.2; Lecture No.: 27

28. Methods of Size Reduction 31 21-06-2024 Unit No.: 1.2; Lecture No.: 28

29. PRINCIPLE: - Impact & inter-particulate Attrition CONSTRUCTION: - Loop of pipe (20 to 200 mm in diameter & upto 2 m in height) form cylindrical grinding chamber made up of S.S. or alloy steel. Fluid (air/ steam/ inert gas) – introduced through nozzles at the bottom of the loop under pressure (25 to 300 PSI (pounds per square inch). 29 FLUID ENERGY MILL 21-06-2024 Unit No.: 1.2; Lecture No.:

30. CONSTRUCTION: - o Premilled coarse b o t tom is fe d of the near t h e mill t h rough a ve n t u ri injector. o There is an classif i er t o o, internal by whi c h li g hter p a rt ic les finer & are hea v ier d ischa r ged a nd part ic les a re retained until reduction to small size. 30 21-06-2024 Unit No.: 1.2; Lecture No.:

31. WORKING: - Material is fed near the bottom of the mill. Material is then exposed to high pressure stream of air or gas & is swept into violent turbulence by the sonic & supersonic velocity of the streams. The particles are accelerated to high speed & they collide with each other, which causes fracture of the particles. The high degree of turbulence causes impact & attritional forces between the particles, which reduce the material to finer state. The finer particles are employed by the drag of gas leaving the mill, while larger, heavy particles are carried downward & back to the grinding chamber. 31 21-06-2024 Unit No.: 1.2; Lecture No.:

32. ADVANTAGES: Simple construction and Easy to operate. Fine particle size can be obtained. There is no moving part in the mill, so no abrasion hence no contamination of the product. The c lassi fi e r , p e r m i t s c l o s e co n t rol o f the pa r ti c le s ize thereby narrow size distribution. For sensitive materials inert gas can also be used. Product is smoother than by any other method. 32 21-06-2024 Unit No.: 1.2; Lecture No.:

33. DISADVANTAGES: High cost. If feed is not controlled the material may choke. If the air fluid is not clean it causes contamination of the product. Premilling is required. APPLICATIONS: Fine powdering Thermolabile materials Dehydration of wet materials Coating of fine particles 33 21-06-2024

34. 21-06-2024 Unit No.: 1.2; Lecture No.: 34

35. 21-06-2024 Unit No.: 1.2; Lecture No.: 35

36. ADVANTAGES OF HAMMER MILL It is rapid in action, and is capable of grinding many different types of materials. They are easy to install and operate, the operation is continuous. There is little contamination of the product with metal abraded from the mill as no surface move against each other. The particle size of the material to be reduced can be easily controlled by changing the speed of the rotor, hammer type, shape and size of the screen.

37. DISADVANTAGES H e at b u i l d u p d u ring m i ll i ng is m o r e , therefore, product degradation is possible. H a mme r m i ll s ca n n o t b e em p l o y e d t o m i ll sticky, fibrous and hard materials. The screens may get clogged. Wearing of mill and screen is more with abrasive materials.

38. BALL MILL These are also knows as tumbling mills. Principle: The ball mill works on the principle of impact between the rapidly moving balls and the powder material, both enclosed in a hollow cylinder . At low speeds, the ball roll over each other and attrition (rubbing action) will be the predominate mode of action. Thus, in the ball mill, impact or attrition or both are responsible for the size reduction.

39. Advantages: It can produce very fine powder . Ball mill is used for both wet and dry grinding processes. Toxic substances can be size reduced , as the cylinder is closed system. In ball mill, installation, operation and labour costs are low .

40. Disadvantages: The ball mill is a very noisy machine. Ball mill is a slow process . Soft, tacky, fibrous material cannot be milled by ball mill.

41. 44 END RUNNER MILL & EDGE RUNNER MILL PRINCIPLE: - Impact & shearing CONSTRUCTION: End Runner Edge Runner Mechanical Mortar & Pestle Mortar-Mixer Mortar made up of Steel or granite Heavy cast iron or granite wheel weighing several tonnes A doumble shaped heavy pestle made of similar material is mounted eccentrically in the mortar. The diameter of the roller may vary from 0.5 to 2.5 meter. The rollers are mounted vertically in a horizontal shaft. Mortar is rotated by a motor. The pestle rotates by friction. Each roll revolves on its own axis, while both travel round a shallow steel or granite base. 21-06-2024 Unit No.: 1.2; Lecture No.:

42. 21-06-2024 Unit No.: 1.2; Lecture No.: 45

43. 21-06-2024 Unit No.: 1.2; Lecture No.: 46

44. 21-06-2024 Unit No.: 1.2; Lecture No.: 47

45. 21-06-2024 Unit No.: 1.2; Lecture No.: 48