IPQC 3: Disintegration and dissolution tests-LAW JIA JUIN

DISSOLUTION MACHINE

DISINTEGRATION TESTER

IPQC 3: Disintegration and dissolution tests

CONTENTS

A.OBJECTIVES

B.RESULTS, TABLETS, AND GRAPHS

C.DISCUSSION

D.CONCLUSION

E.REFERENCES

A.    OBJECTIVES

1.      To measure the disintegration time of the given tablets.

2.      To measure the tablets dissolution time in aqueous media.

3.      To measure the disintegration and dissolution  time variability of different batches of tablets.

B.     REESULTS, TABLES AND GRAPHS

Part 1: Disintegration test

All the 6 sample tablets tested took about 9minutes for complete disintegration. (Disintegration time is within 15 minutes). Hence, we can conclude by saying that the sample tablets tested had passed the disintegration test.

Part 2: Dissolution test

Table 1: Standard Paracetamol solution (calibration curve)

Concentration of Paracetamol /μgml-1	Absorbance (y)/ABS unit
0	0
2.5	0.213
5	0.427
10	0.863
20	1.675

Graph 1: standard graph of absorbance against paracetamol concentration

Standard: Y=M.X+C

M=gradient/slope of the straight line, C= Y -intercept of the straight line                

Y= 0.0839X +0.0067

Table 2: Sample Paracetamol 1

Time(min)	Abs/ ABS unit	Conc (mcg/ml)	DF	Actual Conc (mcg/ml)	Conc. In 3 ml	Conc. in 900 ml	Cumulative amt	Cumul. Amt(mg/900ml)	% drug dissolved
0	0	0	0	0	0	0	0	0	0
5	0.132	1.49	100	149.34	448.03	134410.01	134410.01	134.41	26.88
10	0.293	3.41	100	341.24	1023.72	307115.61	307563.65	307.56	61.51
20	0.254	2.95	100	294.76	884.27	265280.10	266751.85	266.75	53.35
30	0.377	4.41	100	441.36	1324.08	397222.88	399578.90	399.58	79.92

Table 3: Sample Paracetamol 2

Time(min)	Abs/ ABS unit	Conc (mcg/ml)	DF	Actual Conc (mcg/ml)	Conc. In 3 ml	Conc. in 900 ml	Cumulative amt	Cumul. Amt(mg/900ml)	% drug dissolved
0	0	0	0	0	0	0	0	0	0
5	0.329	3.84	100	384.15	1152.44	345733.02	345733.02	345.73	69.15
10	0.315	3.67	100	367.46	1102.38	330715.14	331867.58	331.87	66.37
20	0.385	4.51	100	450.89	1352.68	405804.53	408059.36	408.06	81.61
30	0.321	3.75	100	374.61	1123.84	337151.37	340758.88	340.76	68.15

Table 4: Sample Paracetamol 3

Time(min)	Abs/ ABS unit	Conc (mcg/ml)	DF	Actual Conc (mcg/ml)	Conc. In 3 ml	Conc. in 900 ml	Cumulative amt	Cumul. Amt(mg/900ml)	% drug dissolved
0	0	0	0	0	0	0	0	0	0
5	0.265	3.08	100	307.87	923.60	277079.86	277079.86	277.08	55.42
10	0.304	3.54	100	354.35	1063.05	318915.38	319838.97	319.84	63.97
20	0.374	4.38	100	437.78	1313.35	394004.77	395991.42	395.99	79.20
30	0.354	4.14	100	413.95	1241.84	372550.66	375850.66	375.85	75.17

Table 5: Sample Paracetamol 4

Time(min)	Abs/ ABS unit	Conc (mcg/ml)	DF	Actual Conc (mcg/ml)	Conc. In 3 ml	Conc. in 900 ml	Cumulative amt	Cumul. Amt(mg/900ml)	% drug dissolved
0	0	0	0	0	0	0	0	0	0
5	0.292	3.40	100	340.05	1020.14	306042.91	306042.91	306.04	61.21
10	0.345	4.03	100	403.22	1209.65	362896.31	363916.45	363.92	72.78
20	0.362	4.23	100	423.48	1270.44	381132.30	383362.10	383.36	76.67
30	0.367	4.29	100	429.44	1288.32	386495.83	389996.07	390.00	78.00

Table 6: Sample Paracetamol 5

Time(min)	Abs/ ABS unit	Conc (mcg/ml)	DF	Actual Conc (mcg/ml)	Conc. In 3 ml	Conc. in 900 ml	Cumulative amt	Cumul. Amt(mg/900ml)	% drug dissolved
0	0	0	0	0	0	0	0	0	0
5	0.316	3.69	100	368.65	1105.96	331787.84	331787.84	331.79	66.36
10	0.368	4.31	100	430.63	1291.90	387568.53	388674.49	388.67	77.73
20	0.349	4.08	100	407.99	1223.96	367187.13	369584.98	369.58	73.92
30	0.392	4.59	100	459.24	1377.71	413313.47	416935.28	416.94	83.39

Table 7: Sample Paracetamol 6

Time(min)	Abs/ ABS unit	Conc (mcg/ml)	DF	Actual Conc (mcg/ml)	Conc. In 3 ml	Conc. in 900 ml	Cumulative amt	Cumul. Amt(mg/900ml)	% drug dissolved
0	0	0	0	0	0	0	0	0	0
5	0.325	3.79	100	379.38	1138.14	341442.19	341442.19	341.44	68.29
10	0.357	4.18	100	417.52	1252.56	375768.77	376906.91	376.91	75.38
20	0.351	4.10	100	410.37	1231.11	369332.54	371723.24	371.72	74.34
30	0.361	4.22	100	422.29	1266.87	380059.59	383681.41	383.68	76.74

Table 8: average of percentage drug dissolved and standard deviation

Time(Min)	Mean % drug dissolved	S.D
0	0	0
5	57.88	16.03
10	69.63	6.59
20	73.18	10.15
30	76.89	5.14

 

Graph 2: Dissolution profile

C.     DISCUSSION

            Dissolution and disintegration tests are both important parameters to be tested during both In Process Quality Control (IPQC) and End Process Quality Control (EPQC). Disintegration is a process when the tablets are broken down into smaller particles and pieces. Disintegration should happen first then only dissolution can happen. This disintegration test is important as the disintegration time will directly affect the bioavailability of the tablets The desired disintegration time for un-coated tablets in distilled water or 0.1M hydrochloric acid are within 15 minutes at a temperature of 37⁰C.

Dissolution test is another important parameter to be assessed. Stirred-vessel method had been applied for this test .Dissolution test measures the rate of drugs released from the sample tablets. The values we get can be used for calculations and used to plot a graph of mean percentage drugs released against time, and this graph will become the drug release profile of that particular batch of tablets. From the drug release profile we can then predict the bioavailablity of the tablets produced and make adjustments accordingly. Secondly, the graphs obtained for different batches of tablets can be used to test the reproducibility and uniformity of a certain method of manufacturing.  It is also been used to assess or study the factors that may affect the bioavailability of a certain type of tablet drug.

Graph 1 presents to us the standard graph of absorbance against paracetamol concentration. From graph 1 we can deduce that the absorbance is directly proportional to the concentration of paracetamol.

In this experiment, all the 6 sample tablets tested took about 9minutes for complete disintegration. (Disintegration time is still within 15 minutes). Hence, we can conclude by saying that this batch of tablets produced had passed the disintegration test (According to United State Pharmacopiea ).

            The mean percentage drugs released for the 6 different paracetamols tablets are shown in table 8. There is less than 80% of paracetamol been released (or dissolved) within the period of 30 minutes. Therefore, in order to test whether our batch of tablets had fulfilled with the USP tolerances criteria, a second stage of dissolution test should be carried out.

Acceptance criteria:

1.      Disintegration test:

·        All the non-coated tablets must disintegrate within 15 minutes of commencement of the test.

·        If one or two tablets had fail to disintegrate completely within 15 minutes, the test has to be repeated for 12 additional tablets,

·        ;and not less than 16 of the total of 18 tablet tested should disintegrate completely.

    2.      Dissolution:

Tolerances (USP24):

Not less than 80% (Q) of the labeled amount of paracetamol is dissolved in 30 minutes. The experiment is repeated if the results do not fulfill the USP tolerances criteria.

Stage	Number tested	Acceptance criteria
S1	6	Each unit is not less than Q + 5%
S2	6	Average of 12 units (S1 +S2) is equal to or greater than Q, and no unit is lee than Q -15%
S3	12	Average of 24 units (S1+ S2+S3) is equal to or greater than Q, and no unit is lee than Q -15% and no unit is less than Q-25%

D.    CONCLUSION

1)     This batch of tablets had passed the disintegration test with the disintegration time of 9 minutes (which is less than 15 minutes.)

2)     Less than 80% of paracetamol tablets dissolved within 30 minutes in stage 1. Stage 2 dissolution test has to be carried out.

E.     REFERENCES

·        Wikipedia

·        Online USP

·        E-portal IMU