Partech Midterms LEC 4

Size Enlargement

Size enlargement

It is the process by which smaller particles are put together to form larger masses without changing the original particles identity.

• Pharma

• Agri

• Food

• Minerals

• Metallurgical

• Ceramic

What industries do size enlargement associate itself?

• to reduce caking and lump formation

• to improve flow properties

• to increase bulk density for storage

• creation of non-segregating mixtures of ingredients

• to provide a defined metered quantity of active ingredient

• control of surface to volume ratio in catalyst supports

• production of a useful structural form

• improved product appearance

• control of solubility

• control of porosity, hardness

Why is size enlargement important?

Granulation

One of the size enlargement processes that is utilized in order to improve both flow and compression characteristics.

Agglomeration

It is used in pharmaceutical products for them not to contain or have low amounts of dust to provide increased safety during the handling and processing of toxic or medicinally active materials.

enhances product size and geometry according to desired characteristics for functionality, marketability, and protection from hazards (dust)

What is the application of size enlargement in chemical industries?

Pigments that are micro-agglomerated to become dust-free, smoothly flowing, and withstand handling without degradation.

Example of size enlargement in chemical industry

for handling, protection against dust, producing desired structure, ehancing appearance, and decreasing density

What is the application of size enlargement in food industries?

Instant food products with reduced density to induce improved properties such as quick rehydration

Example of size enlargement, particularly agglomeration, in the food industry

flow, storage, transportation, metering, feeding, and dust production

What is the application of size enlargement in the animal feed industry?

veterinary medicine and milk replacers

Example of size enlargement in the animal feed industry

to make the particle ores into pellets for better handling and reduced dust, as it is required to configure them as tightly packed to restrict airflow

What is the application of size enlargement in mining and metallurgical industries?

storage and handling as well as enhancing fine powder’s flow properties and packing efficiency

What is the application of size enlargement in ceramic industries?

ensures friability, freedom from caking, and improved agrotechnical properties

What is the application of size enlargement in agricultural industries?

mixing and forming enlarged rectangular shapes for building material

What is the application of size enlargement in construction industries?

create pearly and shimmering looks affecting the degree of glimmering

What is the application of size enlargement in cosmetic industries?

less

In cosmetics, the smaller the particle size, the _____ lustrous the powder will be

Bonds

these are formed between powder particles so that they adhere together to form granules, and these bonds must be sufficiently strong to prevent breakdown during handling operations

• Product size

• Granule structure

• Moisture content

• Surface tension of liquid

What are the factors that affect interfacial bondings?

• Van der waals forces

• Forces due to adsorbed liquid layers

• Liquid Bridges

• Electrostatic forces

• Solid Bridges

What are the five mechanisms responsible for interfacial bondings (according to Rumph 1962)?

Van der Waals Forces

These are molecularly based attractive forces between all solids. It happens when momentary dipoles causes induced dipoles when one side of a particle is ever so slightly partially more negative or positive than the other.

0.1 eV, decreases with the sixth power

What is the energy of van der waals forces in order? and it decreases by how much distance between each molecules?

Forces due to adsorbed liquid layer

This interfacial bonding happens when the presence of condensable vapour will have a layer of adsorbed vapour on the surface, such overlapping of layers result to the bonding forces.

area of contact and tensile strength of adsorbed layers

The strength of the bond in forces due to adsorbed liquid layers depend on?

Partial pressure of the vapour in the surrounding atmosphere

The thickness and strength of the layers is directly proportional to the?

Critical partial pressure

At a certain point of _____, the adsorbed layer gives way to the next interfacial bonding called liquid bridges.

TRUE

TRUE or FALSE: Forces due to adsorbed liquid layers are usually negligible in magnitude compared with forces resulting when the proportion of liquid present is sufficient to form interparticle liquid bridges.

Forces due to Liquid Bridges

Presence of liquid on the surface affect particles by smoothing effects, increased particle-particle contact, and effect of reducing the interparticle distance.

Newitt and Conway-Jones (1958)

They identified the four types of lqiuid states depending on the proportion of liquid present between groups of particles

• Pendular

• Funicular

• Capillary

• Droplet

In sequence, what are the four states of liquid bridges?

Electrostatic forces

These are forces resulting from the friction caused by the interparticle collisions and frequent rubbing against equipment surfaces.

Transfer of electrons

What causes the charges of the particles in electrostatic forces?

Electrostatic F = kq1q2/r²

Formula to familiarize in electrostatic forces

TRUE

TRUE OR FALSE: Electrostatic forces do not require contact between particles and can act over relatively long distances compared with adhesional forces which require contact.

Solid bridges

Compared to liquid bridges, these are more permanent and are actually considered the true final stage of the granulation process; the phase in which the liquid has been removed from the original granule.

• crystalline bridges

• liquid binder bridges (dried then formed)

• solid binder bridges

What are the three forms of solid bridges?

crystalline bridges

If the material of the particles is soluble in the liquid added to create the granules, ______ are formed when the liquid evaporates.

Below 1 micron in size

At what size does van der waals forces become important?

Below 80 micron in size

At what size does adsorbed vapour forces become relevant?

Below 500 micron in size

At what size does liquid bridges become active?

• Compaction

• Granulation

• Encapsulation

• Pelletizing

• Agglomeration

What are the common size enlargement processes?

Compaction

The process involving large deformations, large strain, nonlinear material behavior and friction.

Granulation

It transforms a powder material into larger entities to end up with an aggregate considerable larger in szie with a porous structure.

Encapsulation

It is the process whereby various ingredients can be stored within a specific size shell or coating for protection and/or later release.

Pelletizing

It is the process of compressing or molding a material into the shape of pellets.

Agglomeration

Formation of assemblages in a suspension and particles dispersed in the liquid phase stick to each other, and form irregular clusters, flocs or aggregates.

• Bulking agents

• Functional additives

• Colorants, coating aids, stabilizers, pH modifiers, and release rate modifiers

What are the commonly used excepients in size enlargement?

Bulking agents

also known as fillers, they serve to form the core or structure of a dosage form; they are usually inert and relatively inexpensive compared to functional additives

Functional additives

These excepients include binders, disintegrants, lubricants, colorants, and stabilizing agents.

• Drug used

• Process involved

• Formulator

• Excepient cost

What are the factors considered in choosing the excepients?

Sugars and polymers (natural, semisynthetic, synthetic)

What are the common varieties of binders used?

sucrose, glucose and sorbitol

Example of sugar binders

acacia, alginic acid, sodium alginate, gelatin, starch

Example of natural polymers

ethylcellulose, sodium carboxymethylcellulose, methylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose

Example of semisynthetic binders

polyvinylpyrrolidone and PEG

Example of synthetic binders

Khaya gum, Leucaena leucocephala seed gum, anacardium occidentale gum, gellan gum, and a combination of detarium gum and veegum

Example of natural binders

IPA, dichloromethane, chloroform

Examples of binders aside from sugars, semisynthetic polymers, natural polymers, synthetic binders, and natural binders

To provide the cohesiveness essential for the bonding of the solid particles under compaction to form a tablet.

What is the primary role of binders?

Promote size enlargement to produce granules and thus improve flowability of the blend during the manufacturing process

What is the role of binders in wet-granulation processes?

TRUE

TRUE OR FALSE: The cohesive properties of binders may reduce friability of the tablets and thus aid in their durability and elegance

In melt granulation

What is the main application of PEG binders?

In both wet massing and fluid bed granulation

What is the main application of polyvinylpyrrolidone binders?

TRUE

TRUE OR FALSE: agglomeration is the formation of agglomerates or aggregates by sticking together of smaller particles and granulation is agglomeration by agitation

1. Wetting and Nucleation Stage

2. Growth Stage

3. Consolidation Stage

4. Attrition or Breakage Stage

What are the 4 key mechanisms contributing to size enlargement by wet granulation?

Dry Granulation

Dry mixing, Slug and De-slug, and Compaction are processes under what type of granulation?

Aqueous and Non - Aqueous

What are the processes under Wet Granulation?

Wetting and Nucleation Stage

In this process, void between particles is replaced by liquid which is added as liquid drop. This is governed by the surface tension of the liquid and the contact angle with the particles.

Nucleation

This term is typically applied to the initial coalescence or growth of primary particles in the immediate vicinity of the larger wetting drop.

Washburn Equation

The rate at which wetting occurs is important in granulation which is known as _____.

It gives a narrower granule size distribution and improved product quality through better control over the granulation process.

Why is improved wetting more desirable in modulating agents?

• Reduce viscosity

• Increase surface tension

• Minimize contact angle

• Increase the prore size within the powder

How do you increase the rate of wetting?

TRUE

TRUE OR FALSE: A wider particle size distribution will give rise to smaller pores

Drop Controlled Nucleation Regime

This is the condition for when each droplet should land on the powder without touching other droplets and sink quickly into the powder to form a new nucleus granule.

• drop controlled

• shear controlled

• intermediate zone

What are the three nucleation regimes?

• low spray flux (spray density is low and relatively few drops overlap)

• fast penetration time (penetration into the powder must be faster than touching with other drops)

Drop controlled nucleation occurs when one drop forms one nucleus and should occur when there is both?

Powder mixing and shear characteristics will dominate as mechanical dispersion regime.

What happens when either criterion of drop controlled nucleation (low spray flux, fast penetration time) is not met?

The liquid binder can only be dispersed by powder shear and agitation.

What happens in the mechanical dispersion regime?

Granulation Consolidation Stage

In this stage, the granule density is increased caused by closer packing of primary particles.

This is the stage in the granulation process which determines the porosity and density of the final granules

granule saturation (s)

The fraction of pore space filled with liquid.

granule porosity and liquid level

Which parameters controls the granule saturation?

The saturation increases and once it exceeds 100%, further consolidation pushes liquid to the granule surface making it wet. Such wetness causes effects in granule growth rates.

What happens during the granule consolidation stage when the porosity of the particle decreases?

Growth Stage

Due to agitation and dissipation of kinetic energy, granules coalesce by collision and create increased surface area for bonding.

Stokes number

This is the parameter that determines whether coalescence will occur. It is the measure of the ratio of collisional kinetic energy to energy dissipated through viscous dissipation.

TRUE

TRUE OR FALSE: For coalescence to occur, the stokes number must be less than a critical value St*.

• non-inertial

• inertial

• coating

Based on the criterion of critical stokes number, three regimes of granule growth are identified for batch systems with relatively low agitation intensity. What are these?

By coating of primary particles onto existing granules.

Once stokes number is comparable with critical measures, it sort of enters an equilibrium phase where breakage and growth is balanced. How does growth continue in this condition?

Granule Deformation

This is something entailed and accompanied by high agitation intensity systems.

• Steady growth behavior (size increase proportiionally with time)

• Induction behavior (there is long period where size does not increase)

What are the two types of growth behaviour that occur depending on granule deformation?

TRUE

TRUE or FALSE: All types of granule growth can be described using the saturation and deformation stokes number and the granule growth regime map.

Breakage

Also called fragmentation, this is the frature of a granule to form two or more species.

Attrition

Also called erosion, this is the reduction in size of a granule by loss of primary particles from its surface

• increase fracture toughness

• increase resistance to attrition

• make changes to the process

How to control breakage by altering granule properties?

1. Particle rearrangement

2. Particle deformation

3. Particle fragmentation

4. Particle bonding

5. Plastic and elastic deformation

What is the order of mechanism of dry granulation?

Particle rearrangement

This stage of dry granulation occurs initially as powder particles begin filling void spaces.

Air begins to leave the powder blend’s interstitial spaces, and particles begin to move closer together

What happens during particle rearrangement?

Particle Deformation

This is the next stage of dry granulation in which occurs when compression forces are increased.

Plastic deformation

The increased deformation occuring when parricles have contact in points where bonding occurs.

Particle fragmentation

The third stage of dry granulation which follows as the next bonding stage. This occurs at increased compression force levels.

At this stage, particle fracturing creates multiple new surface sites, additional contact points,a nd potential bonding sites.

What happens during particle fragmentation?

Particle bonding

This occurs when plastic deformation and fragmentation occur. It is generally accepted that ____ takes place at the molecular level, and that this is due to the effect of the van der waals forces.