מעבדה לתופעות מעבר תנע, מסה וחום - מצגת מס' 2
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Transcript of מעבדה לתופעות מעבר תנע, מסה וחום - מצגת מס' 2
רגונס חפצי2005
'סמסטר ב
Reactor with Steam Condenser
2
Sulfa :G6PD -רגישות ל. 2
Pharmaceutial Manufacturing Performance
ACTIVE FORMULN FILL PACK
ACTIVE FORMULN FILL PACK
ACTIVE FORMULN FILL PACK
RESEARCH
DEVELOPMENT
MANUFACTURING
TIME
SPACE COST
QUALITY
TIME
SAFETY
Environmental and Social Considerations
Milling & Sieving process in the pharmaceutical industry
Is used for:
Actual sizing
Changing the grain size/grain surface distribution
Density and improving mixing properties.
Variants of mills are available but each type selected depends on the consistency of the raw material while considering the requirements of the finished product.
Particle Size Distribution
Influences of Particle Size
Particle size influences dissolution
Small particles dissolve more rapidly than large ones, which is
important not only in determining the behavior of the drug in vivo
but also in various manufacturing processes.
Particle size influences flow properties of powders
The flow properties of powders are strongly dependent on particle
size and, in particular, particle shape. Since most powders are
moved from one place to another by flowing, control of flow behavior
is highly important. Generally, spherical particles flow much more
easily than elongated particles.
Particle size influences stability of dispersions
The stability of dispersions, such as suspensions and emulsions,
depends on the size of the dispersed material. The forces between
colloidal particles depend on their dimensions, and the settling.
Influences of Particle Size
Effectiveness of drug delivery by Inhalation
Our respiratory systems are incredibly efficient at filtering out particles above a certain
size. Orally or nasally inhaled drug manufacturers must ensure the product is capable of
penetrating the lungs; conversely, cleaning product manufacturers may need to provide
extra controls in order to prevent inhalation if particles are of a dangerous size.
Both tablets and capsules are produced using equipment which controls the mass of
drug and other particles by volumetric filling. Therfore any interference with the
uniformity of fill volumes may alter the mass of drug incorporated into the tables or
capsules. Thus reduce the uniformity of the medicine.
Product appearance
Particle Size Distribution
Particle Size Distribution
The particle size distribution (PSD) may be defined as
“Particle size distribution (PSD) of a powder, or granular material,
or particles dispersed in fluid, is a list of values or a mathematical
function that defines the relative amounts of particles present,
sorted according to size.”
Particle size distribution is also known as grain size distribution.
Particle Size Distribution
Significance of Particle Size Distribution (PSD)
The PSD of a material can be important in understanding its
physical and chemical properties.
It affects the reactivity of solids participating in chemical
reactions, and needs to be tightly controlled in many industrial
products.
So, What is Particle Size?
“Surprisingly, it is not a question that can be easily answered. This is because in the real world, depending upon the material properties, conditions of manufacture and storage, three distinct species will always exist in any powder, wet or dry”.
Particle Size Distribution: Measurement Techniques
There is a wide range of instrumental and other methods of
particle size analysis available. Some of the more common
methods are:
1. Sieve Analysis
2. Sedimentation Methods
3. Elutriation Techniques
4. Microscopic Sizing and Image Analysis
5. Electrical Impedance Method
6. Laser Diffraction Methods
תרופות יכולות להיות:
אבקה או משחה, טבליה: מוצקבמצב.
תמיסה או תרחיף, נוזל טהור: במצב נוזלי.
גז טהור או תערובת גזים: במצב גזי .
Size Reduction
• Raw materials often occur in sizes that are too large to be used and, therefore, they must be reduced in size. This size-reduction mechanical operation can be divided into two major categories depending on whether the material is a solid or a liquid:
• If it is solid, the operations are called grinding and
cutting. • If it is liquid, emulsification or atomization. • All depend on the reaction to shearing forces within
solids and liquids
Size Reduction:
Reduces large solid particles to smaller particles by mechanical means.
Factors affecting size reduction
1. Hardness
2. Stickiness
3. Abrasiveness
4. Temperature
5. Material Structure
6. Moisture Content
7. Physiological Effect
8. Purity Required
9. Ratio of Feed Size to Product Size
SIZE REDUCTION METHODS
There are many different types of size reduction method employed. 1.Cutting methods: used to break down large pieces The material is cut by means of a sharp blade or blades.
2. Compression methods: The material is crushed by application of pressure.
3. A ball mill , fluid energy mills and pin mills are examples of a comminuting method which produces size reduction by both impact and attrition of particles
SIZE REDUCTION METHODS
Three basic mill components:
•All milling equipment have 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
Mill chambers Pin Mill
Milling equipment – impact mills Hammer mills
Medium to coarse size reduction
Peripheral speed 20-50 m/sec
Pin mills
Peripheral speed up to 200 m/sec
Capable of fine grinding
Can be used to mill sticky materials
Ball Mill
Ball Mill - Batch type The ball mill is a cylindrical shell usually filled
to about half its volume with
grinding media (ball).
The balls may be
of metal or porcelain
Continuous ball milling • Conical shell with grinding
media of different sizes • Feed enter from the hallow
end of the mill and milled material exits through coarse screen.
• The outlet is covered with a coarse screen to prevent the loss of the balls
Grinding Ball selection In Grinding, selecting (calculate) the correct or optimum ball size that allows for the best and optimum/ideal or target grind size to be achieved by your ball mill is an important thing for a Processing Engineer
!!!Often, the ball used in ball mills is oversize “just in case”. Well, this safety factor can cost you much in recovery
Grinding Ball selection
Advantages of the ball mill
Ball milling boasts several advantages over other systems: the cost of installation, power and grinding medium is low
It is suitable for both batch and continuous operation, similarly it is suitable for open as well as closed circuit grinding
Applicable for materials of all degrees of hardness
Speed of Rotation 1. At low speeds (a): 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) (c): above the critical speed the mill is said to be centrifuging and grinding of material not occur. 3. At about two-thirds of the critical speed (Optimum speed).
Milling equipment – stirred media mill
Critical parameters
Agitator speed
Feed rate
Size of beads
Bead charge
Density of beads
Design of blades
Mill chamber
Residence time
Mill selection
Wibowo and Ng (1999), AIChE Journal 45 (8) 1629-1648
Particle size reduction
Mixing is more uniform if ingredients are roughly the same size
Milling of wet granules can promote uniform and efficient drying
Increased surface area can improve dissolution rate and bioavailablity
Improved content uniformity of dosage units
Excessive heat generation can lead to degradation, change in polymorphic form
Increase in surface energy can lead to agglomeration
May result in excessive production of fines or overly broad particle size distribution
Benefits
Disadvantages
Sieving - ניפוי