Industrial Pharmacy II 1st Lecture - Size Reduction PDF

Industrial Pharmacy II st 1 lecture size reduction Lecture Objectives Define the terms related to size reduction State the different factors affecting the size reduction process State the objectives of size reduction Differentiate between different size reduction methods...

Industrial Pharmacy II st 1 lecture size reduction Lecture Objectives Define the terms related to size reduction State the different factors affecting the size reduction process State the objectives of size reduction Differentiate between different size reduction methods State the advantages and disadvantages of size reduction Classify the different equipment used in size reduction  Size Reduction Definition Objectives of Size Reduction In the preparation of suspension. It’s the process that To facilitate the mixing of powders. reduces large solid To increase the surface area thus facilitating particles to smaller the solubility of the drug material. particles by mechanical Reduce the bulk of the material to facilitate means. shipping. Materials are crushed to expose cells in case of extraction. 3 3  Factors affecting size reduction 1. hardness 2. Toughness 3. Stickiness 4. Abrasiveness 5. Temperature 6. Material structure 7. Moisture content 8. Physiological effect 9. Purity required 10. Ratio of feed size to product size 4 4  Factors affecting size reduction 1) Hardness It’s a surface property of the material. The harder the material the more difficult it is to reduce in size. Moh’s scale of hardness It is a scale to measure the hardness of minerals as follows: Up to 3 (Soft materials). They can be marked with the fingernail e.g. graphite. Above 7 (Hard materials) They can not be marked with a good knife blade e.g. diamond. Between 3-7 (Intermediate materials). 5 5 2) Toughness It’s often more important than hardness. A soft tough material may present more problems in size reduction than a hard brittle substance, e.g. blackboard chalk is easier to break than rubber. It’s often related to moisture content (compare the toughness of a green herb with the brittleness of a dry one). 6 6  3-Stickiness This property may cause problems in size reduction as: 1. Gummy or resinous materials as myrrh may adhere to the grinding surface. 2. The meshes of screens may become blocked. To solve the problems: Complete dryness of the material or add inert substances such as kaolin. 7 7 4-Abrasiveness It’s a property of hard materials of mineral origin. It has been reported that during the grinding of some very abrasive substances, the final powder has become contaminated with more than 0.1 % of metal from the grinding mill. 8 8  5) Temperature Heat resulting from grinding causes softening of some substances e.g. waxy substances such as stearic acid or drugs containing oils or fats. The high speed of operation of the hammer mill causes the generation of heat that may affect thermo-labile materials or drugs containing gums, fat, or resin. Solution of the problem: 1.Cool the mill either by a water jacket or by passing a stream of air through the equipment. 2.Use of liquefied nitrogen. 9 9  6) Material Structure 7) Moisture Content Some substances are Moisture affects hardness, homogenous in character, but toughness, and stickiness. the majority of them show some Requirements of moisture : special structure e.g. mineral substances may have lines of Dry grinding: Less than 5 %. weakness along which the Wet grinding: More than material splits. 50%. Vegetable drugs have a cellular structure often leading to long fibrous particles. 8-Physiological Effect Some substances are very potent (e.g. hormones) where the small amounts of dust may have a serious effect on the operators. Solution of the problem: 1. Enclosed mills such as the ball mill control the dust and toxic hazards. 2. Applying a special air extraction system. 3. Applying wet grinding, if possible, must be used to avoid dust. 11 11  10-Ratio of Feed Size to Product 9- Purity Required Size Machines that produce a fine product require a fairly small Certain types of size reduction feed size. apparatus cause the grinding Thus it may be necessary to surface to wear, and such carry out the size reduction methods must be avoided if a process in several stages with high degree of purity of the different equipment, e.g. product is needed. preliminary crushing, followed by coarse grinding and then fine grinding.  SIZE REDUCTION METHODS 1. Cutting methods 2. Compression methods The material is cut by means of The material is crushed by the a sharp blade or blades application of pressure 13 13  SIZE REDUCTION METHODS 3. Impact methods: 4. Attrition methods Occurs when the material is The material is subjected to stationary and is hit by an object pressure as in compression but moving at high speed or when the surfaces are moving relative the moving particles strike a to each other, resulting in shear stationary surface. The materials forces which break the particles. shatter into smaller pieces. 14 14  SIZE REDUCTION METHODS 5. Combined impact and attrition methods A ball mill, fluid energy mills, and pin mills are examples of comminuting method that produces size reduction by both impact and attrition of particles. 15 15  Advantages of size reduction in pharmacy 1. Increase surface area which increases the solubility, and dissolution. 2. Enhance the bioavailability. 3. Improvement of extraction rate. 4. Improvement and increasing the drying rate. 5. Improve mixing of materials together so give fewer problems in uniformity of weight. 6. Improve color and/or active ingredient dispersion in tablet excipients. 8. Control particle size distribution of a dry mix to minimize segregation. 16 16  Disadvantages of size reduction in pharmacy 1. A possible change in the polymorphic form of the active ingredient renders it less or totally inactive or unstable. 2. Possible degradation of the drug as a result of heat build-up during milling, by oxidation or adsorption of unwanted moisture. 3. A decrease in bulk density may cause problems in the flowability of material. 17 17  Equipments All milling or Comminution equipment has three basic components: 1. A structure for feeding material to the mill. 2. The milling chamber and its working parts. 3. A receiver or collector in which the milled product is deposited. 18 18  1-Ball mill It is an example of comminuting equipment which produces size reduction by both impact and attrition methods. Types of ball mill A. batch B. continuous C. continuous closed – circuit milling. Another classification of ball mills: 1-Simple 2-Tube mill 3. Harding mill 4. Rode mill 5. Vibration mill. 19 19 A. Batch type The ball mill is a cylindrical shell usually filled to about half its volume with grinding media (ball) in different sizes. The cylinder may be of metal or porcelain. The balls may be of metal or porcelain. The large balls crush the feed and smaller ones form the fine product. The shell is mounted in such a way that it can be rotated on its horizontal longitudinal axis by means of motor- driven rollers. 20 20 Modern ball mill 21 21 B. continuous ball milling Harding Mill It is a conical shell with grinding media of different sizes Feed enters from the hollow end of the mill and milled material exits through the coarse screen. The outlet is covered with a coarse screen to prevent the loss of the balls. 22 22 C. continuous closed-circuit ball milling. It is arranged using the continuous mill with a gas or liquid classifying system. Air and feed enter through the opening at end of the mill. The classifier removes the smallest particles while the larger particles are recycled to the mill inlet for further size reduction. 23 23 C. continuous closed-circuit ball milling. 24 24 Speed of Rotation 1. At low speeds The mass of balls will slide or roll over each other and only a negligible amount of size reduction will occur. 2. At high speed (centrifugation ) At and above the critical speed the mill is said to be centrifuging and grinding of material does not occur. 3. At about two-thirds of the critical speed (Optimum speed) 25 25  Advantages of Ball mill: 1. It is capable of grinding a wide variety of materials of different degrees of hardness. 2. Grinding and mixing occur simultaneously at low labor costs. 3. It is equally suitable for wet or dry grinding. 4. Control of dust and toxic hazards could be achieved. 5. Unstable drugs may be sealed in an inert atmosphere and milled. 6. It can produce very fine powders. 7. It can be used for batch or continuous operation. 9. Grinding also takes place by both impact and attrition of particles. 26 26 Disadvantages of Ball mill: 1. Wear occurs, principally from the balls, but partially from the casing, this may lead to product contamination. 2. Soft or sticky materials may cause problems by caking on the sides of the mill or by holding the balls in aggregates. 3. The ball mill is a very noisy machine, particularly if the casing is of metal. 4. Difficult in cleaning & long milling time. 5. High energy requirements and high cost. 27 27