In Process quality control2, IPQC 2- the content uniformity BY LAW JIA JUIN



PARACETAMOL ASSAYED



THE PHARMACEUTICAL COMPANY CLAIMED THAT THE AMOUNT OF PURE PARACETAMOL PER TABLET IS 500MG



UV SPECTROMETER WE USED



INTERNAL STRUCTURE OF UV SPEC



A MODERN SOPHISTICATED INSTRUTMENT FOR MEASUREMENT OF CONTENT UNIFORMITY.



WRITTEN BY LAW JIA JUIN

Content of this article

1. OBJECTIVES
2. INTRODUCTION
3. CALCULATION
4. RESULTS
5. DISCUSSION
6. CONCLUSION
7. REFERENCES

A.OBJECTIVES

To introduce my reader with the application of content uniformity and also to share with them my experience on the post-manufacturing assessment on the content uniformity of the tablets prepared {the production of tablets had been described in the previous article under pretablet granulation( http://jiajuin0409.blogspot.com/2012/01/pre-tablet-granulation-by-law-jia-juin.html ) and also Tablet production and in process quality control 1, IPQC1 ( http://jiajuin0409.blogspot.com/2012/02/tablet-production-and-in-process.html ) } .

B.INTRODUCTION

In this practical we had learnt to check the variation of active ingredient contained within a batch using an evaluation method known as content uniformity test. It is important for the content uniformity test to be included into the monographs of all coated and uncoated tablets as well as the capsules intended for oral administration. Tablet monographs with a content uniformity requirement do not need to have weight variation requirements.

Content Uniformity Testing is useful for assessing the consistency of powder blends before filling or compressing .In addition to that, it also test the consistency of semi-solid and liquid bulk batches before filling . This test also help the workers to supervise for a proper filling during manufacturing (such as filling of powders into capsules or liquids into vials and bottles) . It also help us to do post manufacturing assessment on the amount of active ingredient contained within individual units for example: Amount of pure paracetamol contained wit.hin individual tablet after compression, is evaluated using this method. Content uniformity testing involves using a content/potency assay to determine the content of active material contained in multiple different samples collected throughout the batch. This test should be carried out along the process of manufacturing, so that any errors happening during the process of manufacturing can be detected early, and adjustment as well as changes can be done immediately to prevent the wastage of raw material and time.

C.CALCULATIONS

Ci)  Assay on 20 tablets

Total Weight of 20 tablets powder = 12.19 g

Weight of pure Paracetamol claimed in 1 tablet = 500 mg

Therefore weight of pure Paracetamol claimed in 20 tablets = 500mg X 20

                                                                                                               =10000 mg = 10 g

Amount of pure paracetamol to be taken is 0.15g (150mg)

10g pure paracetamol <------------------------------->12.19g raw tablet powder

0.15g of pure paracetamol  <-------------------------> B g of raw tablet powder

                                                         B = 0.15 X 12.19

                                                                    10

                                                               

                                                             = 0.183 g

(0.183g of raw tablet powder was needed to gained a 0.15g of pure paracetamol)

Average absorbance we got from the final diluted solution =  (0.367+0.375+0.369) /3 = 0.370 AU

A (1%, 1cm)

1% = 1 gram in 100 ml = 1000mg in 100ml = 10mg/ml of pure paracetamol

715 AU (UV spectroscopy) <--------->10mg/ml of pure paracetamol

The measured absorbance for our final diluted solution is 0.370AU

0.370AU <--------->D mg/ml of pure paracetamol in our sample

D(mg/ml) =   0.370 X 10

                          715

                =   0.00517 mg/ml

The concentration of pure paracetamol in our final diluted solution is 0.00517 mg/ml

Since the dilution factor = 10 X 10

                          = 100

Therefore the actual concentration of pure paracetamol

in our stock solution (before any dilution) is =0.00517X 100 = 0.517mg/ml

0.517mg of pure paracetamol <---------> 1ml of stock solution

Xmg of pure paracetamol <--------->200ml of stock solution

Total amount of pure paracetamol in our stock solution, X =0.517 x200= 103.4mg

Since we know that there is actually 0.183g(183mg) of raw tablet powder been dissolved to make up this 200ml of stock solution (undiluted), we can then deduced that 0.183g of raw tablet powder actually consisting of 103.4mg of pure paracetamol. [Not concise with what is claimed by the manufacturer. The manufacturer actually claimed that 1tablet (0.6g of raw tablet powder) contains 500mg of pure paracetamol and 0.183g of raw tablet powder should contain 0.150mg of pure paracetamol]

%drug variation = [(103.4mg- 150mg)/150mg]x100= -31.1%

C ii) Assay of 5 tablets Individually

Calculation on the % Drug Content Variation

1^st TABLET

Average absorbance recorded= 0.400AU

Concentration of pure paracetamol in final diluted solution

=[(0.400 X 10) / 715] =0.00559mg/ml

Actual concentration of pure paracetamol in stock solution

=0.00559x100(dilution factor)=0.559mg/ml

Pure paracetamol contained in 200ml of stock solution=0.559x200=111.89mg

%drug variation= [(111.89 – 103.4) / 103.4] X 100 = +8.21%

2^nd TABLET

Average absorbance recorded= 0.333AU

Concentration of pure paracetamol in final diluted solution

=[(0.307 X 10) / 715] =0.00466mg/ml

Actual concentration of pure paracetamol in stock solution

=0.00466x100(dilution factor)=0.466mg/ml

Pure paracetamol contained in 200ml of stock solution=0.466x200=93.2mg

%drug variation= [(93.2 – 103.4) / 103.4] X 100 = -9.86%

3^rd TABLET

Average absorbance recorded= 0.401AU

Concentration of pure paracetamol in final diluted solution

=[(0.401 X 10) / 715] =0.00561mg/ml

Actual concentration of pure paracetamol in stock solution

=0.00561x100(dilution factor)=0.561mg/ml

Pure paracetamol contained in 200ml of stock solution=0.561mg/ml x200=112.2mg

%drug variation= [(112.2 – 103.4) / 103.4] X 100 = +8.51%

4^th TABLET

Average Absorbance=0.347AU

[(0.347 X 10) / 715] X 100x200= 97.1mg of pure paracetamol ß---------- short cut

%drug variation =[(97.1 – 103.4) / 103.4] X 100 = -6.09

5^th TABLET

Average Absorbance=0.371AU

[(0.371 X 10) / 715] X 20000 = 103.78mg of pure paracetamol

%drug variation =[(103.78 – 103.4) / 103.4] X 100 =+ 0.36%

D) RESULTS

TAB NO.	WEIGHT	ABSORBANCE/AU (1)	ABSORBANCE /AU (2)	ABSORBANCE /AU (3)	ABSORBANCE /AU (AVERAGE)	% DRUG CONTENT VARIATION
20	12.19	0.367	0.375	0.369	0.370	-31.1%

TABLE 1

TABLET NUMBER	WEIGHT	Average ABSORBANCE/AU	% DRUG CONTENT VARIATION
1	0.61	0.400	+8.21%
2	0.62	0.307	-9.86
3	0.61	0.401	+8.51%
4	0.61	0.347	-6.09
5	0.61	0.371	+0.36%

TABLE 2                   

E) DISCUSSION

According to British Pharmacopoeia, in order to carry out a content uniformity test a representative samples of 30 tablets must be selected out from the batch and 10 out of this 30 tablets are assayed individually. In order for the test to be passed, at least 9 out of 10 tablets must have 85-115% of the labeled drug content (±15%variation only) . And the 10^th tablet should have a variation not more than ±25%.,with 75-125% of the labeled content. If these conditions are not met, the tablets remaining from 30 must be assayed individually & none of them should fall outside the range of 85-115% range, otherwise reject the whole batch.

Due to the time restriction we decided to evaluate only the first 5 tablets instead of doing all the ten tablets .So the result was extrapolated from the 5 tablets tested. Based on the results obtained, we predicted that there were at least 9 out of 10 tablets within the limits of 90-110% of labeled drug content (+/-10% variation) and the 10^th tablet is within the limit of 75-125% of labeled drug content (+/-25%variation ). Therefore, our batch of tablets had passed this content uniformity test successfully. The test was said to have passed (accepted)for the 20 tablets as well as the 5 tablets that were assayed individually. Thus, we can said that the manufacturing process of our tablets are good and well supervised .Each tablet produced contains similar amount of active ingredient with not acceptable variation  ,this can ensure a proper dosing to our patients in the future.

F) CONCLUSION

The Content Uniformity Test is said to have passed for the 20 tablets and also the 5 tablets that were assayed individually, this is because all the five tablets tested individually are within the limit of 85% - 115%.(with variation of +/- 15% ONLY)

G) REFERENCES

1)      www.pharmainfo.net/tablet-evaluation/content-uniformity

       2)   http://asi-rtp.com/content_uniformity_testing_.html