Large Scale Clarification and filtration process

Question 1

Filtration c a n
be broadly
d i v i d e d i n t o?

Answer 1

Solid-Fluid Filtration And Fluid-Fluid Filtration

Question 2

What is solid fluid filtration

Answer 2

This can be defined as the
separation of an insoluble solid
from a fluid by means of a
porous medium that retains
t h e s o l i d b u t a l l o w s t h e fluid t o
p a s s .

Question 3

Solid fluid filtration can be subdivided into

Answer 3

1. Solid-liquid filtration: Involves
   the separation of an insoluble
   material from a liquid.
2. Solid-gas filtration: Separation
   of a solid from air or gas

Question 4

What are the Applications of solid-
Liquid filtration

Answer 4

• Improvement of product appearance
• Removal of potential irritants
• Water purification for
  p h a r m a c e u t i c a l formulation
• Recovery of desired solid material
  from a s u s p e n s i o n
• Recovery of solvents from drug
  s u b s t a n c e manufacturing processes
• Sterilization of t h e r m o l a b i l e
  p r o d u c t s
• Recovery/detection of micro-
  organisms in filtrates after filtration

Question 5

What are the applications of solid gas filtration

Answer 5

Removal of suspended solid material from air to supply purified
air in manufacturing rooms (sterile rooms) or processing
equipment (e.g. fluidized air processors, film coating machinery)
* Removal of particulate matter from the environment during
manufacturing operations (e.g. tableting, coating processes etc

Question 6

Explain Fluid-Fluid Filtration

Answer 6

• This type of filtration can be employed to improve the clarity of a
  pharmaceutical product by removal of dispersed oils (flavouring
  oils may increase the turbidity of a product)
• Removal of entrained oil or water droplets from compressed air.

Question 7

When is compressed air used

Answer 7

Compressed air is used in bottle cleaning, film-coating and fluid
energy mills.

Question 8

What are the M e c h a n i s m s of
F i l t r a t i o n?

Answer 8

1. Sieving/Straining
2. Impingement
3. Filtration by attractive forces
4. A u t o f i l t r a t i o n

Question 9

Explain sieving and straining

Answer 9

M e m b r a n e filters a r e u s e d t o s t r a i n or s i e v e o u t
solid materials from a liquid using filters with
pore sizes t h a t are smaller t h a n the filtrate.
* This technique is used when the contaminant
v o l u m e is l o w or s m a l l v o l u m e s n e e d t o b e
fittered
* Examples of the u s e of membrane filters
include the removal of bacteria and fibres from
parenteral preparations or removal of
contaminants before quantitative analysis
(HPLC, UV/Vis analysis)
* Filtration occurs on the surface of a thin filter.

Question 10

Explain impingement

Answer 10

This has to do with the retainment of suspended
particles between the fibres of a filter medium
* Impingement occurs as a result of the attractive
force between the fiber and the suspended
particle
* If the pores between filter fibres are larger than the
suspended material, some particles would not be
r e t a i n e d
* To enhance retainment, filter media used must be
sufficiently thick to ensure optimal removal of
unwanted materials.

Question 11

What are depth filters and give examples

Answer 11

Filters used in the impingement filtration process are referred to
as depth filters e.g. air filters, oil filters, fuel filters

Question 12

Explain filtration by attractive forces

Answer 12

Electrostatic forces can exert sufficient hold on particles and
r e t a i n t h e m o n a filter m e d i u m
* For example, air can be freed of dust particles in an electrostatic
precipitator by passing the air between highly charged surfaces
which attract dust particles

Question 13

Explain auto filtration

Answer 13

• This refers to a situation where filtered material (filter cake) acts
  a s its o w n filter medium.
• Here, filtered particles accumulate to form residues of varying
  thickness referred to as filter cake. The residue then a c t s a s a filter
  for subsequent liquid

Question 14

Auto filtration is also known as

Answer 14

cake filtration

Question 15

What can be
u s e d to illustrate t h e f a c t o r s t h a t a ff e c t
the rate at which filtration occurs.

Answer 15

The Büchner funnel and flask

Question 15

What are the factors affecting
rate
of f i l t r a t i o n

Answer 15

• The rate of filtration, volume of filtered
  material (m3) obtained in unit time (s),
  can be influenced by the following
  f a c t o r s -
• Area a v a i l a b l e for filtration
• P r e s s u r e difference a c r o s s t h e filter b e d
• Viscosity of the fluid passing through the
  filter
• Thickness of the filter medium and any
  deposited cake

Question 16

The relationship between the factors affecting filtration are described by what equation

Answer 16

𝐾

The relationship between these factors is described in Darcy’s equation –

𝑉
𝑡
=
𝐾
𝐴
Δ
𝑃
𝜇
𝐿
t
V
​
=
μL
KAΔP
​

Where:

V = Volume of filtered material (m³) obtained in unit time (s)
A = Area available for filtration (m²)
ΔP = Pressure difference across the filter bed (Pa)
μ = Viscosity (Pa.s)
L = Thickness of the filter medium (m)
K = The proportionality constant (m³)

K the proportionality constant expresses the permeability of the filter medium and cake and will increase as the porosity of the bed increases.

𝑒
2
5
(
1
−
𝑒
)
2
𝑆
2
K=
5(1−e)
2
S
2

e
2

​

e is the porosity of the cake
S is the surface area of the particles making up the cake

Question 17

How can you increase filtration rate?

Answer 17

Increase the area available for filtration
Increase the pressure difference across the filter bed
Decrease the viscosity of the filtrate
Decrease the thickness of the filter cake
Increase the permeability of the cake

Question 18

List and explain 3 industrial filtration equipment

Answer 18

Gravity Filters: Filtration is driven solely by gravity used mainly in the laboratories.
Vacuum Filters: Used for large scale filtration processes. Filtration is enhanced by vacuum mechanism and continuous cake removal and runs for an extended period e.g. rotary vacuum filters.
Pressure Filters: This large-scale filtration process combines the effect of gravity and pressure to facilitate the separation process. They are the most common type of filters used in the processing of pharmaceutical products. E.g. Nutsche pressure filter, Metafilter, Cartridge filters, Capsule filters etc.

Question 19

Centrifuges are often used in laboratories to

Answer 19

separate solid materials from liquids, but some can be adapted to separate immiscible liquids.

Question 20

What does a centrifuge do?

Answer 20

A centrifuge uses centrifugal force to separate the contents of a sample based on their density.

Question 21

Centrifugation can occur with what two methods?

Answer 21

filtration or sedimentation methods.

Question 22

Two main types of centrifuge are used to achieve separation on an industrial scale which are:

Answer 22

1. Perforated basket centrifuges which perform a filtration-type operation.
2. Tubular-bowl centrifuges where particles sediment towards the wall under the influence of centrifugal force.

Question 23

Explain Perforated Basket Centrifuge

Answer 23

The perforated basket centrifuge consists of a stainless-steel perforated basket lined with a filter cloth.
During centrifugation, the filtrate is forced through the cloth and removed via the liquid outlet, and the solid material is retained on the cloth.

Question 24

What are the applications of Perforated Basket Centrifuges

Answer 24

1. This is used in the separation of crystalline materials from the preparation liquor e.g. preparation of drug crystals like aspirin. 2. Removal of precipitated proteins from, for example, insulin.

Question 25

Explain Tubular-Bowl Centrifuges

Answer 25

Also referred to as centrifugal sedimenters, these consist of a rotating cylindrical bowl. The product enters at the bottom, and the centrifugal force causes the solid to be deposited on the wall as it passes up the bowl and overflows at the top. This can be adapted to separate immiscible liquids.

Question 25

What are the Applications of Tubular-Bowl Centrifuges

Answer 25

1.Liquid-liquid separation 2. Removal of very small particles 3. Removal of solids that are compressible or slimy and which easily block filter media 4. Separation of blood plasma from whole blood 5. Separation of different particle size fractions 6. Examination of the stability of emulsions

Question 26

What is Freeze-drying (lyophilization)

Answer 26

Freeze-drying (lyophilization) is a process used to dry extremely heat-sensitive materials. It can also allow drying of proteins, peptides, blood products, hormones, vaccines without excessive damage.

Question 27

n freeze-drying, the liquid solution or suspension is ___, the pressure above the frozen state is __, and water is removed by ___

Answer 27

frozen, reduced, by sublimation.

Question 28

The phase diagram of water can be used to explain the three steps of the freeze-drying process which are

Answer 28

1. Freezing the solution 2. Reducing the atmospheric pressure above the ice to that of the triple point of the product 3. Adding heat to the system to raise the temperature above the sublimation curve (the line from C to O in the diagram) and provide the latent heat of sublimation.

Question 29

List and explain the Stages of the Freeze-Drying Process

Answer 29

Freezing Stage The solution is cooled to below the normal freezing temperature for pure water, between -10°C to -30°C, but typically below -18°C. Vacuum Application Stage The frozen material is connected to a vacuum to reduce the pressure below the triple point and remove the large volumes of vapour formed during drying. Sublimation Stage In this stage, primary drying occurs by supplying latent heat of sublimation. Secondary heating is applied to completely remove the residual moisture in the container.

Question 30

What are the Advantages of Freeze-Drying

Answer 30

1. Drying occurs at very low temperature, so enzyme action is inhibited and chemical decomposition (e.g., hydrolysis) is minimized. 2. Freeze-dried products are light and porous and therefore dissolve rapidly. 3. Concentration of the product is avoided in freeze-drying, hence, proteins are not denatured. 4. Oxidation is minimized, as the process occurs under a high vacuum, which minimizes contact with air.

Question 31

What are the Disadvantages of Freeze-Drying

Answer 31

1. The porosity, easy dissolution, and complete dryness of the product result in it being very hygroscopic. 2. The process is very slow and uses complicated equipment that is very expensive. 3. Freeze-drying is best reserved for products with high heat sensitivity, which cannot be dried by any other means.

Question 32

What are the Pharmaceutical Application of Freeze-Drying

Answer 32

1. Used for products that cannot be dried satisfactorily by any other heat method, e.g., some antibiotics, blood products, vaccines (BCG, yellow fever, smallpox), enzyme preparations, and microbiological cultures. 2. Used in formulating fast-dissolving tablets. 3. Stabilization of novel drug delivery systems, e.g., liposomes, microparticles, nanoparticles.

Question 33

What is a major problem facing Raw Materials in Nigeria for Pharmaceutical Industry

Answer 33

The Nigerian climate supports a rich diversity of plants and minerals which can be used as locally sourced excipients or pharmacons for the local pharmaceutical industry. Most of these materials are under-utilized because of huge dependence on imported products.

Question 34

How can the government help Raw Materials in Nigeria for Pharmaceutical Industry

Answer 34

Government support through appropriate policies would reduce the dependence of local manufacturers on imports and reduce the cost of medicines in the market.

Question 35

List some Plant-Based Materials

Answer 35

Ginger Turmeric Neem Garlic Aloe vera Casava roots Gums, etc.

Question 36

Nigeria is a significant producer of essential oils, such as

Answer 36

Peppermint oil Spearmint oil Eucalyptus oil

Question 37

Essential oils have various pharmaceutical applications, including

Answer 37

Natural preservatives Anti-oxidants Anxiolytics Anti-inflammatory agents Antimicrobial agents They can also be used as pharmaceutical flavorants

Question 38

nigeria has an abundance of mineral resources, including

Answer 38

Kaolin Limestone Silica

Question 39

Mineral resources can be used as

Answer 39

These can be used as excipients or fillers in pharmaceutical products.

Question 40

Plant based raw materials can be used as

Answer 40

Binders Disintegrants Bulking agents, etc.

Question 41

Nigeria has a significant livestock industry, which can provide raw materials such as

Answer 41

Gelatin Collagen

Question 42

Collagen is used in

Answer 42

1. Topical formulations 2. Supplements to improve skin, bone, and joint health

Question 43

Crude oil can serve as a good source of

Answer 43

1. Solvents: hexane, heptane, dichloromethane, ethanol, methanol, etc. 2. Lubricants: petroleum jelly, mineral oil. 3. Surfactants: polysorbates for emulsions/suspensions. 4. Plasticizers: phthalates used in pharmaceutical packaging materials. 5. Intermediates: benzene, toluene, xylene, etc.

Question 44

What is an effective way of separating solvents from intermediates and active agents.

Answer 44

Distillation and evaporation

Question 45

An important criterion for drug manufacturing is what?

Answer 45

To ensure product purity and consistency.

Question 46

What is the use of evaporators?

Answer 46

To preserve the stability of active therapeutic ingredients while removing impurities, unreacted components, and moisture.

Question 47

There are two main categories of evaporator

Answer 47

Tubular evaporators Plate-based evaporators

Question 48

What is one of the commonly used distillation/evaporation equipment in the pharmaceutical industry.

Answer 48

Tubular evaporators

Question 49

What happens in tubular evaporation?

Answer 49

Samples are introduced at the top of the evaporator above the heated zone and evenly distributed down the vessel wall in a turbulent flow, which creates optimum heat.

Question 50

What are the applications of evaporators

Answer 50

1. Evaporators can be used to concentrate active pharmaceutical ingredients while protecting their stability and biofunctions. 2. Used to remove organic solvents from temperature-sensitive products by distillation. 3. In some cases, evaporators can also help remove excess water to completely dry products, which helps to extend shelf-life and remove impurities down to safe-to-use or -consume levels.

Question 51

What are some considerations for choosing evaporators

Answer 51

1. Evaporation takes place at high temperatures, and the equipment needs to withstand heat, plus chemical corrosion from acids and solvents. 2. The material of the evaporator should not react with samples to avoid biofouling and introducing impurities to the samples. 3. The production volume should determine the size of the evaporator. 4. Use of instrumented equipment will ensure batch-to-batch consistency in drug production.