University of Sulaimani College of Pharmacy Dept. …Pharmaceutical dosage form design •...

University of Sulaimani College of Pharmacy

Dept. of Pharmaceutics5th stage – First Semester

10/9/2019 Industrial Pharmacy I, Dr. rer. nat. Rebaz Ali 1


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


Outlines

• Introduction

• Definitions

• Batch mixing

• Continues mixing

• Mixer selection

• Mechanism of solid mixing


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.


Introduction

Product

Marketing & sale

R & D

Planning & procurement

Quality assurance

Production


Outlines

• Introduction

• Definitions

• Batch mixing


• Mixer selection



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.


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.


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.


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.


Outlines

• Mixing definition and mechanism of fluid mixing

• Batch mixing

• Impeller

• Air jet

• Fluid jet


• Mixer selection



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.


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.


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


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)


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


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.


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


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.


Outlines


• Batch mixing

• Impeller

• Air jet

• Fluid jet


• Mixer selection



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.


Outlines


• Batch mixing


• Mixer selection



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


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).


Roller mill

• Roller mill

• Three roll tube is preferred for semisolid preparations.

• The rollers rotate at different speed.

Scrapper


Outlines


• Batch mixing


• Mixer selection


• Equipment


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.


Outlines


• Batch mixing


• Mixer selection


• Equipment


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!


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.


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.


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)


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


Thank you for your attention!

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