I N S I D E T H I S I S S U E : TABLET AND CAPSULE ...

1 Volume 15. 2015. T H E M A N U FA C T U R I N G P R O C E S S. INSIDE THIS ISSUE: TABLET AND CAPSULE . Unit Operations 2-3. Formulating 3. M A N U FAC T U R I N G. Granulating 4-5 The manufacturing Process was created for companies Milling 5 and individuals to gain a com- plete understanding of the Blending 6 basic requirements needed to make tablets and capsules. Tabletting 7. The objective is that the read- Coating 8 er will gain a quick, yet com- prehensive understanding of Encapsulation 9 solid dosage operations used in the manufacturing process. TABLET Defects 10-11. Packaging 12 The focus will be a step by step explanation of each unit dose operation, common equipment, and practical Objectives in learning knowledge of each operation. understanding the principles The main topics are Formula- of the manufacturing process tion, Blending, Milling, Granu- lation, Drying, Final Blending, enced employee training, the understand each unit of oper- Designed for new employees, Tabletting, TABLET Press Tool- expectation is that having this ation.

2 They should under- recent transfers, Managers, ing, Coating, and Encapsula- information will create a com- stand how machines work QA, R&D, Supervisors, tion. mon denominator; thus pro- and the usage of each piece Leads and Operators ducing an opportunity for of equipment and why one better communication be- technology is preferred over Gain a quick and compre- Common TABLET & CAPSULE tween manufacturing groups. another. hensive understanding of defects and problem solving The company will no longer TABLET manufacturing are also part of the objective. hear that the problem is the fault of another department. Get different departments on Designed for new & experi- The reader should be able to the same page SPECIALIZED TRAINING. IN-PLANT AND PUBLIC SEMINARS. Michael Tousey has devel- agers, R&D, Engineering, tailored to meet the specific oped a complete series of Maintenance, Quality Assur- needs of the customers facili- training programs.

3 Ance, and packaging person- ty and application. nel will all be able to gain knowledge and a better com- These programs can be pre- munication method between All training courses and semi- sented for everyone involved nars can include testing mod- departments. in the manufacturing pro- ules. cess. Operators, Leads, Man- Each of the programs can be Copyright 2015 Techceuticals Page 2 Training Volume U N I T D O S E O P E R AT I O N S. Every separate manufacturing do to make a TABLET out of the Time under pressure is Dwell step is called a Unit Opera- active ingredient. time. TABLET Press speed tion . Weighing, Blending and relates to compressibility and Tabletting are individual unit Powders must Flow; making a time under pressure. Tablets operations. A Batch of TABLET or a CAPSULE requires and capsules must also eject powder or granulation is pro- the powders to be somewhat from the die after being com- cessed in each unit operation.

4 Fluid. Good flow can be com- pressed. The objective is Batch to pared to granulated sugar. Batch Reproducibility in each Bad flow can be compared to Unit Operation. Unit Opera- powdered sugar. Products tions are determined by what must flow freely to achieve manufacturing steps are proper dosage. TABLET press- needed to combine the active es and encapsulation machin- ingredient with other needed ery do not actually weigh the ingredients to make a quality individual dosage amount, finished product. they fill by volume. The three most common Unit Powders must Compress;. Operation pathways are Di- Particles must lock together. rect Compression, Wet Granu- Overly wet particles will cause lating, and Dry Granulating. Sticking. Overly dry particles Which pathway is used de- will cause Lamination. Fine pends on what is needed to particles escape during com- pression. THREE PRINCIPLE METHODS OF DEVELOPING.

5 P OW D E R S F O R T A B L E T M A K I N G. Tablets made by blending the maintained even after the granules . Each granule will dry powdered ingredients liquid is dried and milled. contain a proper mix of the together, and then compress- There are many different ingredients of the formula. ing into tablets is called A types of binders that can be We can control the final den- Directly Compressible Formu- used. sity of the granules by the la . We are saying that the amount of liquid binding solu- All powders have a variety of tion and the mechanical ener- characteristics of these pow- characteristics; some may ders will blend together with gy created by the type of ma- only require a very small chine used. The machines the other ingredients and stay amount of binder and some mixed. This combination of used to blend powders and may require large amounts of add liquid are called ingredients will flow, com- binder.

6 Many powders re- press and eject from the tab- granulators . quire some level of intense let press. Furthermore, the mixing while adding a liquid Some granulators have the TABLET will have good hard- binder, actually comparable ability to dry the excess mois- ness, friability, and will dis- to kneading dough when mak- ture. Many granulators do solve quickly. ing bread. Once the powder not have the ability to dry the If powders will not make a and binding solution are wet massed granulation;. The three principle methods good TABLET because they do kneaded they are then milled therefore the wet granulation not compress, don't flow well, for drying. The bonds that must be moved to the next of developing powders for are too fluffy or separate after hold the particles together unit operation which is called blending, the particles need can withstand the milling Drying. TABLET making are: process forming a uniform to be combined and attached There are many types of Dry- using a pharmaceutical glue size granule.

7 If we accom- plish these unit operation ers that we will discuss later. Direct Compression called a binder. When the When powders are sensitive binder is put into water or a steps correctly (pre-blending, binder addition, milling, drying to liquids, heat, or both, we solvent solution and is must blend the powders with Wet Granulating sprayed or metered into the and final blending) the result is a compressible powder a pre granulated dry binder . powders this process is called If the blended powders will The Wet Granulation Pro- called a granulation. not work with the addition of Dry Granulating cess . The solids within the A granulation is the formation the dry binder and liquid, or liquid solution form bonds of small agglomerates called heat cannot be used, then we between particles which are Copyright 2015 Techceuticals T he M a n u f a c tu r i n g P r o c es s Page 3. (Three Principle Methods ods, the Wet Granulation No Capping continued) method is the most common.

8 It is also the most demanding No Lamination must Dry Granulate . The and requires many unit opera- Dry Granulation method uses No Sticking tions. mechanical force to densify and compact powders togeth- In The TABLET & CAPSULE Pro- Good Friability er which forms dry granules. cess, we will discuss each of This compaction can be done the principle methods and Good Disintegration on a TABLET press using discover the unit operations slugging tooling . Slugging required for each method. Good Dissolution tooling or slugging punches & We will define each pro- dies are a method to dry com- cessing step and the common As we go through each unit pact powders into granules. equipment types used in each operation we will refer to one unit operation. of these three principle pro- The other method is to use a machine called a Roller Com- cessing methods. The final goal is to make a pactor or Chilsonator. This is quality TABLET with the follow- basically the same kind of All formulas have a ing attributes: Direct Compression machine used to make the limit to how fast they charcoal briquettes for our Good Weight Control Wet Granulating outside grill.

9 The slugged or roller compacted powders are Good Thickness Control Dry Granulating can work on a TABLET then milled, final blended and Good Hardness Control press. Even the best compressed on a TABLET press. Of these three principle meth- Good Ejection TABLET press cannot improve this limitation without changes in the THE FORMULA of the TABLET to eject from the press a formula at any speed. formula . TABLET press without falling Each formula has a limit to apart. Excipients also en- how fast it can be com- We have determined that a hance the hardness, disinte- pressed. In order to increase formula contains many ingre- gration, appearance, color, the speed, the formula must dients other than just the taste, and the overall perfor- be changed. active ingredient. The ingredi- mance of the TABLET . ents within the formula in addition to the active are As stated previously, a formu- called excipients. la that is designed on a slow Excipients are needed to speed TABLET press may not make a good quality TABLET at work on a high speed press.

10 The required TABLET press Even the best TABLET press speed. They help the flow, with all the best design fea- compressibility and the ability tures may not be able to com- WHY GRANULATE? To improve powder flow. To improve compressibility. To reduce fines. To control the tendency of powders to segregate. To control density. To capture and fuse small quantities of active material. The average TABLET press speed in the pharmaceutical industry produces 3,000 tpm (tablets per minute) or 50 tablets per sec- ond. TABLET press speeds can exceed 10,000 tpm or 166 tps. Copyright 2015 Techceuticals Page 4 Training Volume G R A N U L E F O R M AT I O N I N T H E W E T. G R A N U LATIN G P ROCE SS. Most of the early research in the binding solution and form granulating took place in pans small granules by pendular and drums and some of the bridging. Continued addition theory and knowledge gained of binding solution and tum- using that equipment is not bling action consolidates and directly applicable in all tech- strengthens the granules nologies.