The Manufacturing Process — Part 1

The Manufacturing Process was created for companies and individuals to gain a complete understanding of the basic requirements needed to make tablets and capsules. The objective is that the reader will gain a quick, yet comprehensive understanding of solid dosage operations used in the manufacturing process.

The focus will be a step by step explanation of each unit dose operation, common equipment, and practical knowledge of each operation. The main topics are Formulation, Blending, Milling, Granulation, Drying, Final Blending, Tabletting, Tablet Press Tooling, Coating, and Encapsulation. Common tablet & capsule defects and problem solving are also part of the objective.

Designed for new & experienced employee training, the expectation is that having this information will create a common denominator; thus producing an opportunity for better communication between manufacturing groups. The company will no longer hear that the problem is the fault of another department. The reader should be able to understand each unit of operation. They should understand how machines work and the usage of each piece of equipment and why one technology is preferred over another.

Specialized training — In-Plant and Public Seminars

Techceuticals has developed a complete series of training programs. These programs can be presented for everyone involved in the manufacturing process. Operators, Leads, Managers, R&D, Engineering, Maintenance, Quality Assurance, and packaging personnel will all be able to gain knowledge and a better communication method between departments.

Each of the programs can be tailored to meet the specific needs of the customers facility and application. All training courses and seminars can include testing modules.

Unit Dose Operations

Every separate manufacturing step is called a “Unit Operation”. Weighing, Blending and Tabletting are individual unit operations. A “Batch” of powder or granulation is processed in each unit operation. The objective is Batch to Batch Reproductibility in each Unit Operation. Unit Operations are determined by what manufacturing steps are needed to combine the active ingredient with other needed ingredients to make a quality finished product.

The three most common Unit Operation pathways are Direct Compression, Wet Granulating, and Dry Granulating. Which pathway is used depends on what is needed to do to make a tablet out of the active ingredient.

Powders must Flow; making a tablet or a capsule requires the powders to be somewhat fluid. Good flow can be compared to granulated sugar. Bad flow can be compared to powdered sugar. Products must flow freely to achieve proper dosage. Tablet presses and encapsulation machinery do not actually weigh the individual dosage amount, they fill by volume.

Powders must Compress; Particles must lock together. Overly wet particles will cause Sticking. Overly dry particles will cause Lamination. Fine particles escape during compression.

Time under pressure is Dwell time. Tablet Press speed relates to compressibility and time under pressure. Tablets and capsules must also eject from the die after being compressed.

Three Principle Methods of Developing Powders for Tablet Making

Tablets made by blending the dry powdered ingredients together, and then compressing into tablets is called “A Directly Compressible Formula”. We are saying that the characteristics of these powders will blend together with the other ingredients and stay mixed. This combination of ingredients will flow, compress and eject from the tablet press.

Furthermore, the tablet will have good hardness, friability, and will dissolve quickly.

If powders will not make a good tablet because they do not compress, don’t flow well, are too fluffy or separate after blending, the particles need to be combined and attached using a pharmaceutical glue called a binder. When the binder is put into water or a solvent solution and is sprayed or metered into the powders this process is called “The Wet Granulation Process”. The solids within the liquid solution form bonds between particles which are maintained even after the liquid is dried and milled. There are many different types of binders that can be used.

All powders have a variety of characteristics; some may only require a very small amount of binder and some may require large amounts of binder. Many powders require some level of intense mixing while adding a liquid binder, actually comparable to kneading dough when making bread. Once the powder and binding solution are kneaded they are then milled for drying. The bonds that hold the particles together can withstand the milling process forming a uniform size “granule”. If we accomplish these “unit operation” steps correctly (pre-blending, binder addition, milling, drying and final blending) the result is a compressible powder called a granulation.

A granulation is the formation of small agglomerates called “granules”. Each granule will contain a proper mix of the ingredients of the formula. We can control the final density of the granules by the amount of liquid binding solution and the mechanical energy created by the type of machine used. The machines used to blend powders and add liquid are called “granulators”.

Some granulators have the ability to dry the excess moisture. Many granulators do not have the ability to dry the wet massed granulation; therefore the wet granulation must be moved to the next unit operation which is called Drying.

There are many types of Dryers that we will discuss later. When powders are sensitive to liquids, heat, or both, we must blend the powders with a pre- granulated “dry binder”. If the blended powders will not work with the addition of the dry binder and liquid, or heat cannot be used, then we must “Dry Granulate”. The Dry Granulation method uses mechanical force to densify and compact powders together which forms dry granules. This compaction can be done on a tablet press using “slugging tooling”. Slugging tooling or slugging punches & dies are a method to dry compact powders into granules.

The other method is to use a machine called a Roller Compactor or Chilsonator. This is basically the same kind of machine used to make the charcoal briquettes for our outside grill. The slugged or roller compacted powders are then milled, final blended and compressed on a tablet press.

Of these three principle methods, the “Wet Granulation” method is the most common. It is also the most demanding and requires many unit operations. In The Tablet & Capsule Process, we will discuss each of the principle methods and discover the unit operations required for each method. We will define each processing step and the common equipment types used in each unit operation.

The final goal is to make a quality tablet with the following attributes:

1. Good Weight Control
2. Good Thickness Control
3. Good Hardness Control
4. Good Ejection
5. No Capping
6. No Lamination
7. No Sticking
8. Good Friability
9. Good Disintegration
10. Good Dissolution

-Michael Tousey, Techceuticals

Find out more about the manufacturing process here.
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