tablet production

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TABLET PRODUCTION

University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh

2University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh

Contents:

1. Layout of facilities. 2. Materials flow. 3. Quality assurance procedures. 4. Design of facilities. 5. Construction consideration. 6. Equipment consideration. 7. Environmental consideration. 8. Material management and inventory control.

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Layout of Facilities:

What is layout?

A plan or design of something that is laid out.

Purpose:

To control cross contamination.

Typical layouts for solid dosage form manufacturing:

1. Perimeter manufacturing, centre warehouse.

2. Circular flow.

3. Straight line flow.


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1. Perimeter manufacturing, centre warehouse: In this type the centre, or core, of the facility is a storage or warehouse area for raw materials,

packaging components, and bulk stocks, with the manufacturing and packaging operations located at the outer perimeter.

Advantage:

Space conservation by virtue of having the supply areas close to the areas being supplied.

Disadvantage:

Chances of contamination or mix up b/c of crossover traffic pattern of material.


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Fig. Perimeter manufacturing, central warehouse. 1) Administrative offices, 2) Receiving area, 3) Receiving quarantine, 4) Tablet coating, 5) Tablet compression, 6) Tablet granulation, 7) Approved materials warehousing, 8) In-process warehousing, 9) Approved bulk materials, 10) Pharmaceutical dispensing, 11) Liquids, creams, ointment manufacturing, 12) Packaging area, 13) Label room operation, 14) Shipping area.

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2. Circular flow: It consists of receiving , approved raw materials and components storage, and dispensing on

one side, with manufacturing, quarantine, bulk stock, and packaging across a central corridor.

Advantage:

Since the flow is circular so it eliminates much of crossover traffic.


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Fig. Circular flow: 1) Administrative offices, 2) Receiving area, 3)Receiving quarantine, 4) Approved materials warehousing, 5) Pharmaceutical dispensing, 6) Tablet granulation, 7) Tablet compression, 8) Tablet coating, 9) Liquids, creams, ointment manufacturing, 10) Approved bulk materials, 11) In-process quarantine, 12) Packaging area, 13) Label room operation, 14) Shipping area.


3. Straight line flow: It consists of basic straight line flow to minimize contamination or mix-up, moving the materials along a critical path. Advantage: Minimal crossover of materials. Disadvantage: Additional space required to accommodate this configuration.


Fig. Straight line flow: 1) Administrative office, 2) Tablet coating, 3) Label room operation, 4) Tablet compression, 5) Tablet granulation, 6) Pharmaceutical dispensing, 7) Approved material warehousing, 8) Receiving quarantine, 9) Receiving area, 10) Liquids, creams, ointment manufacturing, 11) Approved bulk material, 12) In-process quarantine, 13) Packaging area, 14) Shipping area.

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Receiving

Quarantine (First Storage)

Final Storage

Raw Material Dispensing

Package Component Dispensing

Granulation

Compression

Bulk Quarantine

Bulk StockPackaging

Shipping

Material Flow Chart

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1. Receipt of materials.

2. The material should be quarantine-designated and moved to a quarantine area. Quarantining should be carried out by either full physical examination or utilization of suitable paper system.

3. Notification for sampling should occur at the point of quarantine.

4. On notification of release by quality control, materials should be released and moved into final storage area for use. Locator books or sheets should be setup and adherence to the policy of FIFO should be followed.

5. Weighed batch quantities and packaging components are assembled in a staging area.

6. Materials for the batch are moved to granulating area, appropriately verified on manufacturing documents and placed in the mixing equipment.

7. After granulation, material is dried, milled and blended, then stored in an in-process storage area or moved directly to compressing area.

8. Compressing machine may be fed in a variety of ways, including scooping, direct fed from inverted drums, bin fed, etc.

9. The bulk product is collected in appropriate containers and moved to bulk quarantine.

10. On quality control release, the containers are approve-labeled, the yield verified, documentation completed and product moved to bulk stock.

11. Finally, shipping of final product.

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Quality Assurance Procedure

Purchase or manufacture raw material to specifications

Analytical lab Storage of raw material in quarantine area

Transfer of raw material to released area

Calculate and weigh raw material quantities needed for manufacturing

Check working formula procedures and batch file

Analytical lab In-process Checking of equipment and ingredients Analytical lab Complete processing Working formula procedure audit

Packaging Checking of equipment, finished product, labels, containers.

Analytical lab Finished product in quarantine area Batch audit

Analytical lab for Storage in released finished product area Marketing stability monitoring



Design of Facilities:

1. Receiving.2. Dispensing.3. Granulating.4. Design of Granulation Area.5. Tablet Compression.6. Design of Tablet Compression Area.7. Tablet Coating.8. Packaging.9. In-Process Quarantine.10. Approved Stock Storage.


Receiving:

Centralized Warehouse. Cleaning services should be provided for both the sampling area and sampling utensils. It is recommended that separate quarantine, approved storage, rejected storage areas to be provided. Lighting should be adequate.

Typical SOP Format:Department: Warehousing and Dispensing.Procedure: Receiving Operation for Incoming Materials.

1) Receiving Report.2) Receipt of Material.3) Handling of Materials. a. Pharmaceutical Manufacturing Raw Ingredients. b. Pharmaceutical – Packaging Components. c. Tank Truck Deliveries. d. Materials for Special Handling. e. Rejected Materials. f. Nonproduction Materials.4) Partial Deliveries.5) Returned Goods.6) Standing Orders.7) Time Period for Retention of Records.


Dispensing:

A centralized weighing department is recommended.

Ideally the area should be an enclosed facility adjacent to manufacturing area, using approx. the same construction materials utilized in the manufacturing areas.

Adequate recessed lighting (125 fc ).

Proper humidity and temperature control.

Weighing stations should perform diversity of weighing.

The weighing rooms are approx. 10*8*7 ft.

Each room has a self – contained, air – handling unit and moves air from left to right across the work area through perforated plates located on each side of room, at a velocity of 90 to 110 ft/min.

The air should filtered through a bank of prefilters and then through HEPA filters before return to room.

Make up air should be conditioned to maintain a temperature of 75 – 78˚F and returned to room.

An equal amount of air is removed after HEPA filters to maintain room balance.

Weighing is performed in the deepest part of room to prevent any dust migration.


Horizontal laminar flow hoods with bench top are recommended for small quantity weighing (‹1 Kg).

If the operation is small, standard dial or digital readout scales may be used.

For larger operation minicomputerized digital readout weighing systems are used.

Monthly schedule for calibration and inspection of scales by outside scale contractor should be performed.

A washroom for cleaning and storing weighing utensils is also recommended.

Space should be available for storage of weighing batch quantities until they are required in processing areas.


SOP Format:Department: Warehousing and Dispensing.Procedure: Storing and Dispensing of Pharmaceutical Raw Materials.

1. Warehousing and Dispensing Office.2. Pharmaceutical Material Stores. 2.1 Storage Procedures. 2.2 Issuing of Materials for Manufacturing. 2.3 Issuance of Materials to Areas Other than Manufacturing. 2.4 Screening of Materials. 2.5 Weighing of Issued Materials. 2.6 Cleaning of Equipment and General Housekeeping.


Granulating:

Wet Granulation:

Wet granulation has some basic steps in common with dry granulation: a) Comminution. b) Blending. c) Milling. d) Lubrication.

The additional steps necessary are the preparation and addition of a granulation solution, wet screening, and drying.

Granulating liquid may be deionized water, deionized water and alcohol, or other appropriate liquid.

Granulating liquid may be used to introduce binders, such as gums or starches or coloring agents.

After addition of granulating liquid, mixing or kneading continues until uniform dispersion of liquid is attained.

Wet screening or milling may be employed to break up moist mass into appropriate size granules for drying.

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Wet granules are then dried in appropriate racks for oven drying, in pots for fluid bed drying or in other suitable equipment.

Material is then dry screened or milled to achieve desired particle size.

Lubricants may have been included in the wet stage; if not they may be incorporated at this time, prior to final batch blending.

Other procedures for wet granulation may be employed. Basically, all these methods combine wetting the powders to form granules and then drying the granules in the same piece of equipment.

These includes: a) Spray dryer. b) Fluid bed dryer. c) Air suspension technique.



Dry Granulation:

1) Slugging: A tablet press, utilizing flat – faced punches, is used to compact the blend of finely divided powders into large compacted masses known as “slugs”. The slugs then are screened or milled to produce a granular material which can be compressed as tablets.

2) Chilsonator: It turns out a steady, continues flow of compacted mass aggregates resembling a thin cake. The aggregates then are screened or milled to produce granules.

Direct Compression:

It depends on the utilization of material that may be compacted with no difficulty.

It is a simple and less time consuming process.


Design of Granulating Area:

Granulating Room:

It should be preferably 12*22 ft and large enough to accommodate all materials, equipments and personnel.

It should also accommodate drying racks or fluid bed dryer bowls.

It should have:o Sloped floor (1/8th inch. slope per foot) and drain for complete wash down from front to back.o Proper drainage.o Hot and cold potable water.o Steam for equipment washing.o 0.2 micron filtered purified water for final rinsing.

Similar rooms of suitable size should be provided for the milling and sizing and blending operation.

Granulating solutions:

It can be prepared in granulating room or in a centralized granulating solution preparing room.

Centralized granulating solution preparing room should be equipped with:o 0.2 micron filtered purified water.o Explosion free electrical outlets and electrical mixers.o Non slip floor.


Fluidized bed dryers and Drying:

It should be located in separate rooms.

They should be supplied with HEPA filtered air.

It should be available with suitable heat control and recording devices.

In case of overnight drying there should be installment of a temperature limit alarms.

Solid reduction, milling, grinding equipment should be allocated to enable mesh patterns or particle size determination to be made against a standard.

A centralized washing facility should be provided in granulating area for cleaning portable equipment.

A proper storage area for equipment and utensils should be provided.


Reference:

1) Liebermen.H.A; Lachman.L; “Pharmaceutical Dosage Form: Tablets”; Vol. 3; 1982; Page.277 – 297.

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tablet production

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