chapter: Unit operations process size reduction and size seperation

unit operation

1. Unit operations Ms. Manjusha H. Charde

2. contents Definition Objective/ applications, Principles Construction and working of- Size reduction : Hammer mill, ball mill Size Separation: Cyclone Separator, sieves and standards of sieves Mixing: Double cone blender, turbine mixer, triple roller mill Filtration: Membrane filter and sintered glass filter Drying: Fluidized bed dryer and process of freeze-drying Extraction

3. INTRODUCTION The pharmaceutical industry uses various unit operations such as size reduction, size separation, drying, filtration, extraction, etc to process materials to convert them into products. Unit Operations gives ideas about science related to specific physical operations; different equipment design, construction, and operation material; and calculation of various physical parameters (mass flow, heat flow, mass balance, power and force, etc.).

4. Size reduction Size reduction or comminution is the process of reducing large solid unit masses into small unit masses, coarse particles, or fine particles. Size separation (or Classification) Size separation (or classification) is a process in which particles of desired size are separated from other fractions.

5. Objectives 1. Size reduction leads to an increase in surface area. Example-I: The rate of dissolution of solid drug particles increases many folds after size reduction. Griseofulvin, an antifungal drug, when administered in its micronized form shows around five times better absorption. Example II: The absorptive power of charcoal and kaolin increases after size reduction due to an increase in surface area. 2. Size reduction produces particles in a narrow size range. Mixing powders with a narrow size range is easier. 3 . Pharmaceutical suspensions require finer particle size. It reduces the rate of sedimentation. 4. Pharmaceutical capsules, insufflations (i.e. powders inhaled directly into the lungs), suppositories , and ointments require particle size to be below 60 µm size.

6. Factors affecting size reduction

7. 1) Hardness Hard materials require more force to break down compared to soft materials due to their higher hardness level. 2) Toughness Tough substances such as rubber pose greater challenges for size reduction compared to hard and brittle substances like chalk. 3) Stickiness Difficulty in size reduction arises from stickiness, as the material adheres to the grinding or sieve surfaces of the mill. 4 ) Material structure Materials having special structures may create a problem during size reduction. e.g. vegetable drugs having cellular and fibrous structures are difficult to break.

8. 5)Moisture content The presence of excessive moisture in the material makes the process of size reduction difficult. Material with 5% moisture in the case of dry grinding and 50% moisture in the case of wet grinding does not create any problem. 6) Softening temperature The process of size reduction can generate heat which may cause difficulties during the process. 7) Purity required Impurities may be imparted to the product by grinding surfaces during the size reduction process. 8) Physiological effect During the size reduction of a potent drug, dust is produced which may affect the operator, hence to avoid this , enclosed mills may be used.

9. Hammer mill Principle: It works on the principle of Impact i.e. material is more or less stationary, it is hit by an object moving at high speed. Construction: It consists of a metal casing enclosing a central shaft to which four or more swinging hammers are attached. The lower part of the casing consists of a screen through which a material is passed and collected out when a desirable degree of size reduction is achieved. The shaft is rotated with an electric motor. The speed of the motor is 1000 to 5000 rpm.

10. Working : The material is put into the hopper, which is connected to the drum. The material is reduced to small size due to the fast rotation of hammers. When the material achieves the desired size , it passes through the screen . Advantages: It can be easily cleaned . The speed and screen can be easily changed. It is simple to install and operate. It can be operated under a closed system to reduce dust and explosion hazards. Disadvantages Sticky material chokes the screen. Due to high-speed operation, heat is generated which may affect thermolabile drugs. Gums, resins and fatty materials are avoided. Application It is used for producing intermediate grades of powder from almost all types of substances.

11. Ball Mill Principle : Ball mill works on the principle of combined impact and attrition. In the ball mill, the particles receive impact from the ball or pebbles and attrition as the balls slide over each other. Construction: It consists of a hollow metallic cylinder mounted on a metallic frame rotated on its longitudinal axis. The cylinder contains balls made of metal, rubber or porcelain which occupy 30-50% volume of the mill. The ball size depends upon the feed size and the mill’s diameter. The cylinder has a diameter of about 1 to 3 meters.

12. Working: The drug to be ground is out into a cylinder of the mill and is rotated. The speed of rotation is very important. At low speed (fig. A) ball slides over each other, while at high speed (Fig. B) due to centrifugal force, the ball will be thrown to the walls and hence no size reduction occurs. But at optimum speed (fig. C) balls are carried almost to the top and then fall in, which results in size reduction of the particles. After a suitable time, the material is taken out and passed through a sieve to get the powder of the required sieve. The particles of about 200 mesh can be obtained.

13. Advantages It can produce a very fine powder. Capable of grinding a wide variety of materials of different characters. It is suitable for both wet and dry grinding. It is easy to clean. It can be used for continuous operation by attaching a classifier with the mill. Low operative cost and simple installation. Maintenance is easy. Can be sterilized and so used in parenteral and ophthalmic preparation. Disadvantages It is a noisy machine. Wear occurs from balls and casing which may cause contamination of the product. Soft and sticky materials may cause problems in the grinding process in the ball mill. Applications Ball mill is used to grind brittle drugs into fine powders.s

14. Size separation Size separation is a unit operation that involves separating a mixture of various-sized particles into two or more portions using screening surfaces. Size separation is also known as sieving, sifting, and screening. This technique is based on physical differences between the particles such as size, shape, and density.

15. OBJECTIVES / APPLICATION OF SIZE SEPARATION To determine particle size for the production of tablets and capsules. To improve the mixing of powders. To improve the solubility and stability of particles during production. To optimize feed rate, agitation, and screening during production To control the quality of raw materials. To be Useful in the production of tablets, capsules, suspensions, emulsions, ophthalmic preparations, ointments, creams, etc

16. OFFICIAL STANDARDS FOR POWDERS The Indian Pharmacopoeia has laid down the standards for powders for pharmaceutical purposes. The I.P. specifies five grades of powder which are as under -

17. COARSE POWDER A powder of which all! the particles pass through a sieve with a nominal mesh aperture of 1.7 mm (No. 10 sieve) and not more than 40.0 percent through a sieve with a nominal mesh aperture of 355 µm (No. 44 sieve) is called coarse powder. MODERATELY COARSE POWDER A powder of which all the particles pass through a sieve with a nominal mesh aperture of 710 µm (No. 22 sieve) and not more than 40.0 percent through a sieve with a nominal mesh aperture of 250 µm (No. 60 sieve) is called moderately coarse powder. MODERATELY FINE POWDER If all the particles of a powder pass through a sieve with a nominal mesh aperture of 355 µm (No. 44 sieve) and not more than 40.0 percent through a sieve with a nominal mesh aperture of 180 µm(No. 85 sieve), it falls in this group.

18. FINE POWDER If all the particles pass through a sieve with a nominal mesh aperture of 180 µm (No. 85 sieve), it is called fine powder. VERY FINE POWDER If all the particles of the powder pass through a sieve with a nominal mesh aperture of 125 µm (No. 120sieve), it is said to be very fine p owder.  

19. sieves Sieves are made of wire cloth with square meshes woven from uniform circular wires of suitable materials. Ensure no reaction between the sieve material and the substance being sifted. Standards for sieves used for testing must specify the following: Number of sieves Nominal size of aperture Nominal diameter of the wire Approximate percentage sieving area Tolerance of average aperture size. Nominal size of aperture

20. MECHANISM OF SIZE SEPARATION The working of mechanical sieving devices is based on any of the following methods .

21. Sieving method In this method, the fine powder is separated from the coarse powder using sieves of desired number. The degree of fineness of a powder can be determined by passing it through a sieve. Sieves are numbered to distinguish them from each other. Construction and working To separate the particles of a powder based on their size, a set of sieves is used. These sieves are placed in a descending order, meaning the sieve with the largest openings is placed at the top, and the one with the smallest at the bottom. The sieve at the bottom is connected to a receiving pan.. The material is placed in the uppermost sieve. The sieves are shaken with the help of a mechanical sieve shaker or electromagnetic devices. It helps the particles to pass through the sieves

22. Sieve shaker machine

23. Advantages I nexpensive Easy to use Disadvantages Chance of clogging of sieve if powder is not properly dry During shaking, attrition may occur.

24. Cyclone separator Principle The centrifugal force is used to separate solids from fluids. The separation depends not only on the particle size but also on the density of particles. Hence , depending on the fluid velocity, the cyclone separator can separate all types of particles or remove only coarse particles , allowing fine particles to be carried through with the fluid. Construction It consist of a cylindrical vessel with a conical base. Upper part of the vessel consists of a tangential inlet and a fluid outlet. Solid outlet is fitted at the base.

25. Working The suspension of a solid in gas (usually air) is introduced tangentially at a very high velocity, so that rotary movement takes place within the vessel. The particles are subjected to a centrifugal force due to the rotational flow in the cyclone separator.. The solids are thrown out to the walls, thereafter they fall to the conical base and are discharged out through a solids outlet.

26. Uses Cyclone separators are used to separate the suspension of a solid in a gas (air).   It can be used with liquid suspensions of solids

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