Industrial Pharmacy 2 - Milling PDF

Pharmaceutical technology 1 INDUSTRIAL PHARMACY 2 Milling By Dr. Amira Mansour  Milling- Introduction Few materials used in pharmaceuticals exist in the optimum size. Most raw material may contain lumps that cannot be processed as such and must be reduced in siz...

Pharmaceutical technology 1 INDUSTRIAL PHARMACY 2 Milling By Dr. Amira Mansour  Milling- Introduction Few materials used in pharmaceuticals exist in the optimum size. Most raw material may contain lumps that cannot be processed as such and must be reduced in size during the production of a dosage form. The term milling is used in the context of size reduction of solid materials. Milling is the mechanical process of reducing the particle size of solids. It’s equivalent to grinding and comminution. Importance of particle size control Particle size can affect texture and aesthetic appearance. Also, many physicochemical properties of dosage forms are affected. For example: 1- In liquid dosage forms, the dispersion of the material in the liquids In suspension, the sedimentation and redispersion is affected by the particle size. 2- In solid dosage forms as tablets and capsules, the flow and compressibility of powder also depend on particle size 3- The separability of the semi-solid preparations as creams and ointments is affected 4- Large particles can cause irritation in the ophthalmic preparation so the particle size should be low  Factors Influence Milling 1- Hardness of the material Hardness or softening of materials influence the choice of equipment used for milling, and also determined its ability to resist size reduction. 2- Abrasiveness of the material is the ability of a material that causes it to be worn out when friction is applied. If the grinding material is abrasive, the chances of contamination with metal particles will be high due to worn out of metal during processing 3- Sticky materials Increased stickiness causes the increased adherence of the material to the grinding mills and failure of the procedure 4- Porous nature of the materials Fibrous materials, cannot be crushed by pressure or impact as they are converted to flakes. So, they must be cut. Flakes Friable materials (sucrose), may be milled by crushed by any pressure process. 5- Moisture content Presence of water more than 5%, often produce stick mass upon dry milling, that is may be affect the process. As; Increase moisture decrease rate of milling Crystalline substance: at low temperature liberate water of crystallization, causing clogging of the mill. Hygroscopic materials: (CaCl2), adsorb moisture and form wet mass, that will stick and clog the mill. 6- Temperature: Heat during milling, soften and melts materials with a low melting point. Examples: waxes, and resins become soft and plastic so stick to the mill Heat-sensitive drugs may be degraded Pigments, may change their shade of color, if the milling temperature is excessive. So, these issues are resolved by cooling the mill  Main structure of mills Feed Grinding Discharge Channel Mean Channel Feed Channel: The material is introduced into the mill through feed channel. Grinding Mean: The size of material is reduced by rotating blades or other means of grinding. Discharge Channel: gives off the reduced particles.  Adjustments of Milling A- Standard adjustments Speed, screen size, design of rotor and load. B- Special adjustments This includs: 1- Atmosphere: Hygroscopic (tendency to absorb moisture) material are milled in a closed system supplied with dehumidified air (air without moisture content). Oxidizable and combustible materials, should be milled in a closed system with inert atmosphere of CO2 and nitrogen. 2- Temperature Control: Small percentage of energy of milling is used during operation. The bulk of energy converted to heat As the heat raise the temp. of the materials, some materials will be affected (melt, decomposed or explode) Prevention is done by removing heat The milling chamber should be cooled by means of cooling jacket or a heat exchanger. 3- Pre-treatment: Pretreatment of fibrous materials with highly pressure rolls or cutters facilitates comminution. 4- Subsequent treatment: This is done, if the extreme control of size is required. It’s necessary to recycle the large particles, either by simply screening the discharge and returning the oversize particles for a second milling. Types of Milling 1-Dry Milling Depends on particle-on-particle contact to reduce the size It’s recommended when the materials undergoes physical or chemical change in water, when the output is required to be dry or when the drying process of the wet product is costly Ex. Sucrose extraction and milling Disadv.: not suitable for dusty materials as they will spread allover the place causing sever contamination  2-Wet Milling Wet grind eliminates dust hazards. It’s usually done in low speed mills which consume less power. Addition of dispersing agent may facilitate size reduction. Once the milling process is complete, these particles are ready for use or can be dried and separated for incorporation into additional products. reduce the product into finer particles, compared to the dry milling Ex. Corn fibers used in cereals production, baked and dairy products  Methods of Size Reduction 1- Cutting ▪Small scale: knife and root cutter. ▪Large scale: Cutter Mill Cutter Mill Consists of: 1-two types of knives. (Rotating knives are attached to a rotor and moving against stationary knives in the casing). 2- Lower part consist of screen, so that the material is retained in the mill until a sufficient degree of size reduction has been obtained. Application: extraction of drugs from tough parts as roots, woods. Adv.: Simple, cheap Disadv.; Material cannot be reduced to fine particles, and the produced particles are coarse in size. Cutter mill is difficult to clean after use so there is risk of contamination. 2- Compression Applying of force/pressure to reduce the particles size ▪Small scale: pestle and mortar that are suitable for small quantities ▪Large scale: Roller Mill  2- Compression Roller Mill Use of 2 cylinder rollers made of stone or metal, placed horizontally, and rotating opposite to each other Usually one roll is driven directly, while the second runs free. The material to be milled is placed in the space between the 2 rollers. To control the size of the product, The Gap between the rolls, the speed of the rollers and the feed rate are adjusted. Application: Crushing seeds prior to extraction, production of semi-solid preparations as creams and ointments Roller Mill Feed Product  3- Impact ▪ Small scale: pestle and mortar. Large scale: Hammer Mill Consists of a high-speed rotor to which swinging hammers are attached. The substance is crushed by repeated impact action of the hammers and the grooved grinding chamber walls. The perforated metal screens retain coarse materials for further grinding while small-sized particles pass through. The final size is controlled by hammer speed and the hole size of screen  Uses: size reduction of almost all types of materials (barks, leaves, roots, crystals, filter cakes); therefore, it is widely used in pharmaceutical industry. Besides, hammer mill is also used for the size reduction of both wet and dry granulation excipients prior to formulation of compressed tablets Advantages: 1- It is rapid action, and has the ability to grind different types of materials. 2- The product can be controlled by variation of rotor speed, hammer type, size and shape of mesh/screen. 3- No surface move against each other, so there is no contamination of the product with the metal of the mill.  Disadvantages: It is not suitable for heat-sensitive materials because at high operation speed it generates heat. There is a need for optimization of the rate of feed to avoid choking of the mill Due to high speed operation, hammer mill is susceptible to damage by foreign objects such as stones or metal in the feed.  Cutter mill Hammer mill Mechanism of size reduction used to cut the materials used to shatter the materials by impact Material properties The materials should be fibrous. The materials should be brittle. Advantages Breaks down large particles; Enable production of fine particles Disadvantages unable to produce fine particles, Not recommended for the fine can’t be used for friable materials grinding of very hard and abrasive (sucrose) material due to excessive wear  4- Attrition: Multiple drive roller mill (Triple roll mill) It consists of 2 or 3 rolls of metal or porcelain, positioned horizontally with a small adjustable gap between the rolls. The rolls rotate opposite to each other at different speeds so that the material is sheared as it passes through the gap. The material is transferred from the slower to the faster roll and finally it is removed by scraper. Uses: Size reduction of solids in suspensions, pastes, ointments.