Post on 01-Mar-2020
transcript
University of Sulaimani College of Pharmacy
Dept. of Pharmaceutics5th stage – First Semester
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 1
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 2
Outlines
1. Principles of pharmaceutical processing
• Mixing
• Milling
• Drying
2. Pharmaceutical dosage form design
• Preformulation
3. Pharmaceutical dosage forms
• Sterilization
Reference: the theory and practice of industrial pharmacy by Leon Lachman
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 3
Outlines
• Introduction
• Definitions
• Batch mixing
• Continues mixing
• Mixer selection
• Mechanism of solid mixing
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 4
Introduction
• The pharmaceutical industry produces, develops, and markets drugs
licensed for use as medications.
• Pharmaceutical companies can deal in generic or brand medications.
• They are subjected to a variety of laws and regulations regarding the
patenting, testing and marketing of drugs.
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 5
Introduction
Product
Marketing & sale
R & D
Planning & procurement
Quality assurance
Production
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 6
Outlines
• Introduction
• Definitions
• Batch mixing
• Continues mixing
• Mixer selection
• Mechanism of solid mixing
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 7
Mixing
• Mixing may be defined as an operation in which two or more components, in
a separate or roughly mixed condition, are treated so that each particle lies
as nearly as possible in contact with a particle of each of the other
ingredients.
Objectives
1. To make simple physical mixture, as in production of tablet, capsules,
creams and etc.
2. Physical changes as preparation of solutions.
3. Dispersion
4. Promotion of reaction.
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 8
Types of mixing
1. Positive
• They are formed from materials such as gases or miscible liquids, which mix
spontaneously and irreversibly.
2. Negative
• After mixing, the components will tend to separate out.
• Energy must be continuously input to keep the components in dispersed
state like Calamine lotion.
3. Neutral
• They are static in their behavior, the components having no tendency to mix
spontaneously, nor do they segregate when mixed, like ointments, paste,
mixed powders.
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 9
Mechanisms of liquid-liquid mixing
1. Turbulent mixing: it characterizes by random fluctuation of the fluid velocity
at any given point within the system
• The fluid has different velocities at different locations at the same time.
• Turbulent flow can be visualized as a composite of eddies of various
sizes.
• An eddy is a portion of fluid moving as a unit in a direction often
contrary to that of the general flow.
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 10
Mechanisms of liquid-liquid mixing cont.
2. Laminar mixing: (streamline) is frequently encountered when highly viscous fluids
are being processed.
• It can also occur if stirring is relatively gentle.
• The velocity components at a given point in the flow field remain constant.
3. Bulk transport: is the movement of a relatively large portion of the material from
one location in the system to another by means of paddles or blades.
4. Molecular diffusion: is the primary mechanism for mixing at the molecular level
resulting from the thermal motion of the molecules.
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 11
Outlines
• Mixing definition and mechanism of fluid mixing
• Batch mixing
• Impeller
• Air jet
• Fluid jet
• Continues mixing
• Mixer selection
• Mechanism of solid mixing
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 12
Batch mixing
• Batch mixing: a system for batch mixing commonly consist of two
components:
1. A tank or other container suitable to hold the material being mixed,
2. A means of supplying energy to the system so as to bring about rapid
mixing.
• Power may be supplied to the fluid mass by means an impeller, air
stream, or liquid jet.
• Baffles, vanes or ducts also are used to direct the bulk movement
of material so as to increase their efficiency.
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 13
Batch mixing
Factors affecting the flow pattern of liquids:
• Form of impeller and its position; e.g. whether it is high or low in the
vessel, whether mounted centrally or to one side, or whether the shaft is
vertical or inclined.
• Container shape.
• Presence of baffles.
• Liquid properties.
• High viscosity, such as paste, will
need a D/d ratio of 1 and low
speed of rotation.
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 14
Impellers
Mixing equipment for liquid
1. Impeller: is the rotating part of a machine which imparts energy to the
liquid to be moved.
• The distinction between impeller types is often made on the bases of type of
flow pattern they produce, or on the basis of the shape and pitch of the
blade.
• Three basic of flow may be produced:
Tangential Radial Axial or
longitudinal
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 15
Impellers cont.
A. Propeller mixers
• The propellers are small impellers that produce a
longitudinal movement of liquids.
• They generally operates at high speeds: up to
8000 rpm.
• Propeller mixer is not normally effective for liquids
of high viscosity.
Vortexing and its remedies
• Due to the high speed of the propellers, air may get
entrapped which may be difficult to remove from
the product.
fig (a) fig (b)
fig (c) fig (d)
fig (e)
fig (f)
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 16
Impellers cont.
B. Turbine mixers
• A turbine mixer uses a circular disc impeller, to which are attached a number
of vertical blades, which may be straight or curved.
• The blades are usually flat, and the liquid moves rapidly in a radial direction.
• They can deal with more viscous liquids than the propeller mixer
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 17
Impellers cont.
C. Paddle mixers
• Paddle mixers consists of flat blades attached to a vertical shaft and rotating
at low speed (50-100 rpm).
• Their blades have a large surface area in relation to the tank in which they
are employed, a feature that permits them to pass close to the tank walls
and effectively mix viscous liquids or semisolids, which tend to cling to these
surfaces.
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 18
Impellers cont.
• Baffles: they are auxiliary devices for directing the flow of the fluid.
• Sidewall baffles, vertically mounted in cylindrical tanks
• They are effective in eliminating excessive swirl and further aid the
overall mixing process by inducing turbulence.
Baffles
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 19
Batch mixing
2. Air jets: buoyancy of the bubbles lifts liquids from the bottom to the top of
the mixing vessel.
• The liquids must be of low viscosity, non-foaming, un-reactive with the
gas employed, and reasonably nonvolatile.
3. Fluid jet: used when liquids are to be pumped into a tank for mixing.
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 20
Outlines
• Mixing definition and mechanism of fluid mixing
• Batch mixing
• Impeller
• Air jet
• Fluid jet
• Continues mixing
• Mixer selection
• Mechanism of solid mixing
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 21
Continuous mixing
• Continuous mixing: is an uninterrupted supply of freshly mixed material
and is often desirable when very large volumes of material are to be
handled.
• Types:
• In a tube or pipe through which the material flows and in which there
is very little back flow or recirculation,
• In a chamber in which a considerable amount of holdup and
recirculation occur.
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 22
Outlines
• Mixing definition and mechanism of fluid mixing
• Batch mixing
• Continues mixing
• Mixer selection
• Mechanism of solid mixing
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 23
Mixer selection
• Factors that must be taken into consideration include:
1. The physical properties of the materials to be mixed such as density, viscosity,
and miscibility
2. Economic considerations regarding processing, e.g. time required for mixing
and the power expenditure necessary.
3. Cost of equipment and its maintenance.
• Monophase systems: Fluids of relatively low viscosity are best mixed by methods
that same time circulate the entire mass of material.
• For this, air jets, fluid jets, and the various high-speed impellers can be used.
• Thick creams, ointments, and pastes are of such high viscosity that it is difficult to
generate turbulence within their bulk and relied on laminar mixing.
• Mixing of such fluids may be done with turbine of flat blade design
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 24
Mixer selection
• Polyphase systems: the mixing of systems composed of several liquid or
solid phase. In a general, the processes of homogenization, suspension
formation, and emulsification may be considered forms of mixing.
• The mixing of two immiscible liquids requires the subdivision of one of the
phases into globules, which are then distributed throughout the bulk of the
fluid.
• The interfacial tension of the globules tends to resist the distortion of
globules shape that necessary for fragmentation into smaller globules
• Forces of shear act to distort and ultimately disrupt the globules
(homogenizer).
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 25
Roller mill
• Roller mill
• Three roll tube is preferred for semisolid preparations.
• The rollers rotate at different speed.
Scrapper
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 26
Outlines
• Mixing definition and mechanism of fluid mixing
• Batch mixing
• Continues mixing
• Mixer selection
• Mechanism of solid mixing
• Equipment
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 27
Segregation
• Powders that have high cohesion forces have more resistant to mixing.
• Surface charge and adsorbed substances such as moisture among factors
that increased cohesiveness.
• Particulate solids tend to segregate because of difference in their size,
density and shape.
• It is most pronounced with free-flowing powders and less with cohesive
powders.
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 28
Outlines
• Mixing definition and mechanism of fluid mixing
• Batch mixing
• Continues mixing
• Mixer selection
• Mechanism of solid mixing
• Equipment
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 29
Tumbling mixer
• Used for mixing / blending of granules or free-flowing powders
• It consists of a container of one of several geometric forms, which is
mounted so that it can be rotated about an axis.
• The tumbling motion is accentuated by means of baffles or simply by shape
of the container.
• Examples like drum, cubical-shaped, double-cone and twin shell blenders
• Tween shell is the most efficient one!
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 30
Tumbling mixer cont.
The efficiency of tumbling mixers is highly dependent on the speed of rotation.
• Rotation that is too slow does not produce the desired intense tumbling
or cascading motion, nor does it generate rapid shear rates.
• Rotation that is too rapid tends to produce centrifugal force sufficient to
hold the powder to the sides of the mixer and thereby reduce efficiency.
• The optimum rate is 30 to 100 rpm.
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 31
Agitator mixer
• This type of mixers employs a stationary container to hold the material and
brings about mixing by means of moving screws, paddles or blades.
• Use: Since the mixing process does not depend on gravity as do the
tumblers, it is useful in mixing wet solids, sticky pastes etc.
• Ribbon mixer
• It consists of horizontal cylindrical tank usually opening at the top and fitted
with helical blades.
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 32
Nautamixer
• Conical orbital screw mixer (Nautamixer)
• It consists of a conical vessel fitted at the base with a rotating screw, which is
fastened to the end of a rotating arm at the upper end.
• The mixer thus combines convective mixing and shear mixing
Motor
Rotating arm
Helical conveyor
Discharge
Fig. Conical orbital mixer (Nautamixer)
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 33
Summary
Mixer
Solid
Tumbler Agitator Nautamixer
Liquid
Impeller
Propeller Turbine Paddle
Air jet Fluid jet
• Disc • ↑ blades • ↑ viscous
• 2 blades • ↓ speed • ↑↓ viscous• Dissolution app.
Baffles
• Different geometry
• Efficiency depends on speed
• Gravity
• Different geometry
• Efficiency depends on speed
• Stationary container
• Moving blade orscrew
• Ribbon mixer
• Conical container
• Rotation screw
• ↑ speed • ↓ blades • ↓ viscous
10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 34
Thank you for your attention!