Tablet production and in process quality control part1 IPQC1 BY LAW JIA JUIN

BY LAW JIA JUIN

Contents of this article

A.    Introduction

B.     Apparatus, materials and procedures

C.    Readings, results and calculation

D.    Discussion

E.     Conclusion

F.     references

A)    INTRODUCTION

Last week my group members and I learnt to use the tabletting machine and spraying kit.

In this report I am discussing on the 1)mechanism of tablet formation,    2) the tableting and spraying machine that we used and also     3)the In Process Quality Control (IQC). Besides that I also bring out the    4)problem faced during tableting, the causes and     5)the remedies to overcome them

Tablet formation is done through compression. Compression is a process in which a force is applied to pack the powders together and reducing the volume of solid particles so that they may be confined within a small limited space. What happens during compression is, energy applied forces particles into close proximity to each other this enables the particles to cohere into porous, solid specimen of defined geometry. The tableting process is sometimes known as “compaction cycle” and can be divided into three stages namely die filling, tablet formation and tablet ejection.

What happens in die filling is the gravitational forces will cause the flow of the powder from a hopper into the die. But before this the die is closed at its lower end by the lower punch. Sometimes the centrifugal forces is also applied to fill the die.

The second step is tablet formation , in which the upper punch is lowered down and enters the die compartment ,the powders filled is compressed until a solid tablet is formed. In this stage the lower punch can be stationary or moving upward. After the maximum force is applied, the upper punch leaves the powder/tablet by moving upward, at the same time the lower punch is also moving upward.

The lower punch rises up until its’ tip reaches the top of the die compartment .The tablet is thus pushed and ejected out from the die compartment. This is called tablet ejection stage.

During tablet formation, the powder particles are repacked, deformed and fractured. In repacking process the powders are rearranged and packed closer, the space between small particles are reduced. There are two types of  deformation, the deformation can be elastic deformation or plastic deformation. Elastic deformation is reversible, which means that the tablet form is subjected to expansion upon removal of upper punch

In plastic deformation the forces of compression is larger than the elastic limit (yield value) leading to irreversible deformation or a deformation not immediately reversible upon removal of the applied force.

In some cases ,fracture of powders particles can occur especially for those brittle powders this is known as “brittle fracture”,  the smaller fragments formed can fill into air spaces between larger granules,  leading to bulk volume reduction.

 There are two types of tabletting machine  ,which are single punch press and rotator press. The single punch press is usually used for small scale production or for standardization and sample testing before a mass production. The rotary press is also referred as multiplication  press was developed to increase the output of tablets. The primary use of this machine is thus during scale up in the latter part of the formulation  work and during large scale up production. These are what we used last week. 

Rotary press                                   single punch press

The tablets formed were coated and coloured by using a dye sprayer.The spraying specification are shown below:

Spray cycle:                                                             Spray 30 sec stop 30 second

Spraying air pressure:                                              2.7 kg/cm²

Dry air Temperature                                                60 ⁰C

Coating Pan Speed                                                            8-10 rpm

Spraying method                                                     Spraying gun                       

These condition must be fulfilled in order to optimize the coating. The sprayer consist of a controller, round rotating compartment, a sprayer with pump, dye reservoir and a hot air pipe for drying.

The in process quality control IPQC is a set of operational techniques and activities taken based on the quality assurance system in order to make sure that all the criteria and requirements have been fulfilled, and the quality of product stated is verified. So why should we carry out this IPQC? The purpose of this IPQC is to adjust ,correct and optimize the parameters within an operating range. IPQC is also carried out so that we are able to inspect the quality of a finished product this is to determine whether the product is acceptable, otherwise the criteria of production are modified before mass production, this can prevent wastage of resources. The screening is done during the production not after the completion of products.

There are four IPQC that we had done last week, which were hardness, friability, weight variation, and disintegration time. I am going to introduce the definition of them as well as their method of assessments under the DISCUSSION part.

B)    APPARUTUS  ,MATERIALS AND PROCEDURES

<AS WRITTEN IN PRACTICAL MANUAL>

C)    RESULTS  ,READINGS and CALCULATION of our EXPERIMENT

Formulation of our tablets

Ingredients	Amount (mg)	Calculate for 500 tablets (g)
Paracetamol	150	75
Starch	2	1
Methyl Cellulose	50	25
Talc	5	2.5
Magnesium stearate	5	2.5

Weight per tablet= 212mg

1.      Hardness :2.8 kg/cm²

2.      Friability : 0.5%

3.      Disintegration : 8 minutes

4.      Weight variation :

Tablet Number	Weight of individual Tablet(gm)	Weight Variation (%)
1	0.1976	+/-3.37
2	0.2070	+/-1.22
3	0.2068	+/-1.22
4	0.2064	+/-0.92
5	0.2072	+/-1.32
6	0.2133	+/-4.30
7	0.2060	+/-0.73
8	0.2048	+/-0.15
9	0.2011	+/-1.66
10	0.2003	+/-0.59
11	0.1916	+/-6.31
12	0.1977	+/-3.33
13	0.2163	+/-5.77
14	0.2049	+/-0.20
15	0.1993	+/-2.54
16	0.2050	+/-0.24
17	0.2051	+/-0.29
18	0.2045	+/-0.00
19	0.2070	+/-1.22
20	0.2071	+/-1.27
Average weight	4.089/20=0.2045(percentage diff should be +/-7.5)
Number of tablets outside the limits		None, all are within +/- 7.5
Batch passes or fails ?		Passes

    

 D) DISCUSSION

There are four IPQC that we had done last week, which were hardness, friability, weight variation, and disintegration time.

Hardness is also known as crushing strength, it is an assessment on the resistance of the tablet to chipping, abrasion, or breakage under the presence of external factors eg forces and heat energy during manufacture, storage, transportation, and handling.

The hardness is dependent on the compression force, die fill, lubricant used, binder used and also the setting of tableting machine. The control of hardness is critical this is because the disintegration and dissolution of tablet is dependent on the hardness of tablets. Besides that, an optimum hardness also enable proper storing and handling of tablets.

The hardness tester used by us during the process of tablet formation is known as stokes-Monsanto , which works by compression force. Before we start using it the reading is adjusted to zero. This is done by placing the tablet in the jaw with help of index finger and thumb of left hand The screw is then rotated clockwise so that the tester itself can hold the tablet. After this adjustment the tester is ready to use. Place a sample tablet and compress it until it break , the reading(kg/cm²) on the tester give us the hardness of tablet.  This test was repeated on minimum 10 tablets and the average of was taken as the hardness of this batch. Oral tablets normally have a hardness of 4 to 8 or 10 kg/cm².

Next I am going to introduce the second IPQC that I did. Friability is defined as the percentage of weight lost by the tablets due to mechanical action eg abrasion and friction. Both abrasion and friction caused tablets to chip, cap ,break or crack slightly. The weight loss due to abrasion and friction is calculated using the initial weight minus the final weight. In our experiment 20 tablets were weighed and placed in Roche Friabilator. This Roche friabilator then was switched on and started to rotated, it induced abrasion and friction to the tablets ,the tablets underwent shock as they fell 6 inches upon each rotation. The friabilty was then calculated by :

(initial weight of 20 tablets- final weight of 20 tablets)/ initial weight of 20 tablets

According to British Pharmacopeia ,tablets should not lose more than 1% of their total weight (BP,USP). Otherwise adjustment is needed.

            The third IPQC test is disintegration time. The apparatus used for disintegration testing is known as Basket-rack assembly. It consist of 6 open ended transparent tubes each 7.7±0.25 cm long and having inside diameter 21.5 mm. Six tablets are placed into basket-rack assembly and connected to the disintegration apparatus. 6 tablets were placed into basket-rack assembly and connected to the disintegration apparatus. Apparatus and timer were started simultaneously. All of the tablets were let inside the water for complete disintegration .All the tablets need to disintegrated completely before the timer was stopped. If 1 or 2 tablets fail to disintegrate completely repeat the test on 12 additional tablets. The time of complete disintegration should be less than 30 min, this is because the tablets are coated before this test was carried out.

            The last IPQC test I am discussing here is weight variation.

Weight variation %=< (average weight-weight of individual tablet)/average weight> x 100%

The smaller the weight variation means that the tablet formation is uniform during compression, this also tell us that the dose of each tablet are standardized. The average weights of our tablets are 204.5mg which is between 130mg and 324mg, so the percentage of weight variation should be +/- 7.5.

In our experiment, the hardness is 2.8kg/cm² . This is too low, outside the optimum range (4 to 8 or 10 kg/cm²). This may be due to incomplete compression , and can be overcome by adjusting the compressing machine to increase the hardness of tablets. In our experiment we also saw that tablets formed underwent some problem like chipping. Chipping is defined as the breaking of tablet edges, while the tablets are leaving the press or during subsequent handling and coating operation. This can be a direct effect of granules which are too dry and I suggested that hygroscopic binder and water should be added into the formulation to slightly moisten up the granules. Besides that we also saw colour variation on a few tablets right after coating by sprayer. This might be due to the migration of soluble dyes plasticizer or uneven spraying. And I suggested that a different plasticizer and mild drying condition should be applied to overcome this problem. Beside that the spraying condition should be properly monitored to address this problem. The rough and hard granules  are due to the mistake that we did in the previous practical, since we added talc and magnesium stearate into the powders before adding the binder. This is a human error and can be avoided the next time, since we learnt from mistake.

E)    CONCLUSION

1.      Weight per tablet= 212mg

2.      Hardness :2.8 kg/cm²

3.      Friability : 0.5%

4.      Disintegration : 8 minutes

5.      Weight variation is acceptable and within the range of +/-7.5

6.      Hardness of our tablets can be improved by adjusting the compression strength of the punches of tabletting machine

F)     REFERENCES

1.      Wikipedia.com.my

2.      Elearning.imu.edu.my

3.      Pharmaceutics-info.com.my

THANK YOU