DRYING AN IMPORTANT UNIT OPERATION OF PHARMACEUTICAL INDUSTRY

ABDUL MUHEEMM.PHARMA 2ND YR(PHARMACEUTICS)JAMIA HMADRAD

CONTENT-

• Introduction

• Purposes

• Period of drying

• Classification of dryers

• Special types of dryers

• references

INTRODUCTION TO DRYING PROCESS Drying can be described by three

processes operating simultaneously:1. Energy transfer from an external source to the

water or organic solvent Direct or Indirect Heat Transfer

2. Phase transformation of water/solvent from a liquid-like state to a vapour state

Mass Transfer (solid characteristics)

3. Transfer vapour generated away from the API and out of the drying equipment

Drying APIs is an important operation for the production of consistent, stable, free-flowing materials for formulation, packaging, storage and transport

Particle attrition or agglomeration can result in major differences in particle size distribution (PSD), compressibility and flow characteristics

Equipment selection Drying specifications

Purpose: To reduce the moisture level of wet granules

What are the problems What are the equipment

Why do it

Over drying (bone dry)

Excess fines

Possible fire hazard

Direct Heating Static Solids Bed Dryers

Direct Heating Moving Solids Bed Dryers

Fluid Bed Dryer

Indirect Conduction Dryers

To keep the residual moisture low enough (preferably as a range) to prevent product deterioration

Ensure free flowing properties

PERIODS OF DRYING

•Warm up period :A-B

•Constant Rate Period (B-C)

HT dependent

•Falling rate period (C-D)

MT dependent

DRYERS IN THE PHARMA INDUSTRY

Dryers can be classified according to: Heat transferring methods

Direct: Fluidised, Tray, Spray, Rotary Dryers, etc.. Indirect: Cone, Tumble, Pan Dryers, etc…

Continuous/ Batch processing Continuous: large quantities/small residence time Batch: small quantities/ long residence time

TRAY DRYERS

a batch tray dryeR consists of a stack of trays or several stacks of trays placed in a large insulated chamber in which hot air is circulated with appropriately designed fans and guide vanes.

It is possible to convert the batch tray dryer into a continuous unit. Figure shows the so-called Turbo dryer, which consists of a stack of coaxial circular trays mounted on a single vertical shaft. The product layer fed onto the first shelf is leveled by a set of stationary blades, which scratch a series of grooves into the layer surface. The blades are staggered to ensure mixing of the material.

ROTARY DRYERS

The cascading rotary dryer is a continuously operated direct contact dryer consisting of a slowly revolving cylindrical shell that is typically inclined to the horizontal a few degrees to aid the transportation of the wet feedstock which is introduced into the drum at the upper end and the dried product withdrawn at the lower end.

VACCUM DRYERS For drying of granular solids or slurries, vacuum

dryers of various mechanical designs are available commercially. They are more expensive than atmospheric pressure dryers but are suited for heat-sensitive materials or when solvent recovery is required

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FLUID-BED DRYERS (FLUIDIZED-BED DRYERS

•Concept of fluidization •Gas velocity realizing the change from stationary(fixed) bed into fluidized bed is called the critical fluidized velocity ucritical. •When gas velocity is increased to the particle free setting velocity u0 , the particle will be carried over, u0 is called the carried over velocity ucarried. ucritical<uoptimum<ucarried

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•CHARACTERISTICS OF FLUID-BED DRYERS: ADVANTAGES:HIGH HEAT AND MASS TRANSFER RATES; SIMPLE STRUCTURES; LOW FABRICATING COSTS; CONVENIENT MAINTENANCE; HIGHER THERMAL EFFICIENCY THAN PNEUMATIC CONVEYING DRYERS; DRYING TIME CAN BE CHANGED; APPLIED TO DRYING OF GRANULAR MATERIALS. •DISADVANTAGES: STRICT OPERATION AND CONTROL REQUIREMENTS; MULTI-SEPARATELY FLUIDIZED COMPARTMENTS(PLUG FLOW DRYERS) HAVE COMPLEX STRUCTURES AND GREAT FLOW RESISTA

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Horizontally separately fluidized compartments (Fig. 5-25) can get even drying and relatively low flow resistance.

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(3)PNEUMATIC CONVEYING DRYERS

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Characteristics: 1)Great contacting area between air and solids;Higher heat transfer and mass transfer rates; Short drying time(0.5~2s). 2)Stable operation and fine product quality.

3)Applying to thermally sensitive and easily oxidized materials.

Defects: Materials easily broken; great flow resistance; high drying duct. (about 30m)

FREEZE DRYER

Highly heat-sensitive solids, such as some certain biotechnological materials, pharmaceuticals and foods with high flavor content, may be freeze dried at a cost that is at least one order-of-magnitude higher than that of spray drying – itself not an inexpensive drying operation. Here, drying occurs below the triple point of the liquid by sublimation of the frozen moisture into vapor, which is then removed from the drying chamber by mechanical vacuum pumps or steam jet ejectors. Generally, freeze drying yields the highest quality product of any dehydration techniques

BASIC ISSUES FOR PHARMACEUTICAL FREEZE-DRYING 7.1.1 New Dosage forms of pharmaceutical drugs According to its development, pharmaceutical

dosage form can be divided into the following generations： The first generation : simple ointment, pill and powder for

oral administration and external use. The second generation: the tablets, injections, capsules and

aerosols made by mechanical and automatic machines. The third generation: slow-release or controlled-release

dosage forms that form a new drug delivery system (DDS) . The fourth generation:targeted dosage forms that form a

targeted drug delivery system. The fifth generation: the automatic release dosage forms

inside the body when the patients have a serious illness. At present, the third and fourth generations of

dosage forms are most concerned by scientists.

In order to realize these new drug delivery system, many new techniques are developed in the formulation of dosage form, such as solid dispersion, inclusion, emulsion, liposomes, microencapsulation.

7.1.3 BASIC PROCESS OF BIOLOGICAL DRUGS FREEZE-DRYING

The technical procedures of drug freeze-drying consist of four processes: preparation and freezing, primary drying (sublimation drying), secondary drying (desorption drying) package.

The temperature, vacuum for each process have to be controlled precisely.

The freeze-dried drugs are dry and porous solids. They can be stored in room temperature or in

refrigerator for a long time.

1. Preparation and freezing of drugs In order to form a stable porous structure after freeze

drying, the concentration of drug solution must be a specific value.

Excipients should be added into the low dose thermal sensitive drugs (hormone, enzyme, vaccine) to reinforce the structure of freeze-dried products.

Lyoprotectant should be added into the biological protein-type drugs or slow-release drugs with bio-membrane to protect proteins from denaturation and the bio-membrane from damage.

The end temperature of pre-freezing must be lower than the glass transition temperature (Tg) or eutectic temperature (Te) of the drug solution.

2. Primary drying (sublimation drying) are performed at low temperature and vacuum. The drying progresses gradually from the surface

to the center of the products. The pores or channels formed by the sublimation

ice become the ways of vapor to escape. The boundary between drying layer and frozen

layer is known as the sublimation interface. The temperature of the sublimation interface is a

critical parameter to be controlled in primary drying process.

90% water in drugs is removed after primary drying.

In primary drying process, the temperature of frozen layer must be lower than Te or Tg’.

The temperature of dried layer must is lower than the collapse temperature (Tc).

The temperature of the heater in the drying chamber should be controlled strictly.

3. Secondary drying (desorption drying) purpose : to remove a portion of the

bound water. The moisture content of drugs is lower than 3%

after secondary drying. Because of large absorption energy, the

product temperature in secondary drying must be increased high enough to remove the bound water, and on the other hand, this temperature cannot induce denaturation of proteins and deterioration of biological drugs.

The Tg of the products increases gradually with the decrement of water in secondary process.

So the drying temperature of the products can be increased gradually, but cannot be higher than Tg.

4. Encapsulation process When the secondary drying process is

complete, plugging system in the chamber is used directly to plug the vials in order to prevent the freeze dried drugs from oxidation and water absorption.

The encapsulation can also be completed after filling nitrogen gas into the chamber.

7.1.4 CHARACTERISTICS OF FREEZE-DRYING TECHNOLOGY FOR DRUGS

characteristics of freeze-drying technology for drugs are can prevent the active components in from

denaturation or loss of biological activity. can protect the components in drugs from

oxidation. can greatly reduce the loss of volatile

components in drugs. can inhibit the growth of microorganism and

the activity of enzyme in drugs.

Freeze dried drugs will maintain the original structure.

Freeze dried drugs have good rehydration property.

Freeze dried drugs can be stored at room temperature for a long time

The initial cost of freeze-drying equipment is larger. Freeze drying is a time and energy consuming process.

It is very difficult to control the parameters at optimum level.

7.1.5 CRITICAL PROBLEMS OF FREEZE-DRYING IN DRUGS

1. Temperature Control and identification of drying procedures Frozen drugs will melt, collapse or crimple if the

temperature is higher than the optimum temperature.

if the temperature is too low, refrigeration load will causing excessive energy consumption and the

sublimation rate will be decreased greatly

2. Cooling Rate in freezing process freezing process determines the drying

rate and the quality of freeze-dried product.

The optimum cooling rates vary with different biological agents.For instance,

slow freezing is usually beneficial to protein polypeptide-type drugs.

Fast freezing is usually beneficial to the virus and vaccine.

3. Types and concentration of lyoprotectant The molecular structure of the active

components is different for different biological agents.

The types and concentration of lyoprotectants required in freeze drying are also different.

Up to now, there is not a universal lyoprotectant applied to all of the biological agents.

DRYER FOR SLURRY AND SUSPENSION

SPRAY DRYER

DRUM DRYERS In drum dryers, slurries or pasty feedstocks are dried

on the surface of a slowly rotating steam-heated drum. A thin film of the paste is applied on the surface in various ways. The dried film is doctored off once it is dry and collected as flakes (rather than powder).

BAND DRYER

For relatively free-flowing granules and extrudates that may undergo mechanical damage if they are dispersed, band dryers are a good option. It is essentially a conveyor dryer wherein the band is a perforated band over which the bed of drying solids rests. Drying air at rather low velocities flows upwards through the band to accomplish drying.

TUNNEL DRYER In this simple dryer concept, cabinets, trucks or trolleys containing

the material to be dried are transported at an appropriate speed through a long insulated chamber (or tunnel) while hot drying gas is made to flow in concurrent, countercurrent, cross-flow or mixed flow fashion. In the concurrent mode, the hottest and driest air meets the wetted material and hence results in high initial drying rates but with relatively low product temperature (wet-bulb temperature if surface moisture is present).

MICROWAVE (MW) AND RADIO FREQUENCY (RF) DRYING

Unlike conduction, convection or radiation, dielectric heating heats a material containing a polar compound volumetrically, i.e., thermal energy supplied at the surface does not have to be conducted into the interior, as limited by Fourier's law of heatconduction. This type of heating provides the following advantages:

· Enhanced diffusion of heat and mass · Development of internal pressure gradients which

enhance drying rates · Increased drying rates without increasing surface

temperatures · Better product quality

REFERENCES

AULTON PHARMACEUTICS : THE DESIGN AND MANUFACTURE OF MEDICINE

CLASSIFICATION AND SELECTION OF INDUSTRIAL DRYERS Arun S. Mujumdar

DRYERS FOR PARTICULATE SOLIDS, SLURRIES AND SHEET-FORM MATERIALS Arun S. Mujumdar

Thanks