CONTENT OF IBUPROFEN

Objectives :To determine the content of ibuprofen whether it tally to the value stated.

Procedures :

1.      20 Ibuprofen Tablets were weighed and powdered.

2.      A quantity of powder containing 0.5 g ibuprofen (0.977g) was extracted with 20 ml chloroform for 15 minutes and filtered.

3.      The residuewas washed with 3 × 10 ml chloroform and gently the combined filtrate was allowed to evaporate just to dryness in a current of air. The residue was dissolved in 100 ml with ethanol (96%) previously neutralized to phenolphthalein solution.

4.      The solution was titrated with 0.1M sodium hydroxide to end point with phenolphthalein solution as the indicator. The content of ibuprofen was calculated to determine that if each ml of 0.1M sodium hydroxide is equivalent to 0.02063 g of C₁₃H₁₈O₂.

Calculation :

Weight of weighing boat + powder (20 ibuprofen tablet)	10.9963g
Weight of weighing boat	3.1796g
Weight of powder (20 ibuprofen tablet)	7.8167g

Calculation to get 0.5g ibuprofen,

1 tablet contains 200mg of ibuprofen and the other excipients.

Hence, 20 tablets contain 4000mg (4g) ibuprofen.

Thus, 0.9770g of powder was weighed and dissolved in 20ml chloroform.

Results :

C₁₃H₁₈O₂  +NaOH                        C₁₂H₁₇COONa + H₂O

The end point of titration= 14.6 mL

Number of mole of sodium hydroxide needed to react with ibuprofen,

N_NaOH= Volume x Molar Concentration

               = 14.6mL x 0.1M

               = 0.00146 mol

From the chemical equation,

Number of mole of ibuprofen  Number of mole of sodium hydroxide used

N_Ibuprofen = 0.00146 mol

Mass of ibuprofen,

Mass_Ibuprofen=  Number of mole x Molar mass of C₁₃H₁₈O₂

                    =  0.00146mol x (13x12.01 + 18x 1.008 + 2x16.00)g mol^-1

                    =  0.00146mol x206.274 g mol^-1

                    =  0.30116 g

                    0.3012g

Discussion :

From the experiment, 0.3012g of C₁₃H₁₈O₂was neutralized by 14.6ml of 0.1M NaOH.

Percentage of deviation =×100
                                    = × 100

                                    =  60.24%

The experimental value is highly deviated from the theoretical value, some random or systemic errors might occur. It is because the acceptable range for the content deviation is between 85%- 115% but the experimental value is only 60.24%. Supposedly, the experiment should be repeated by using a new batch of ibuprofen as serious random or systemic error might have occurred. However, due to time limitation, the experiment was not repeated. For instance, fine powder of ibuprofen may escape as they are too light and easily dispersed in the air. Hence, this may cause loss of active ingredient in ibuprofen and affect the final result. Next, the fine powder cannot be transferred completely from one apparatus to another (for example from pestle to weighing boat), some powder may adhere to the inner wall of apparatus and results in inaccurate amount of ibuprofen weighted. Other than that, parallax error may occur during taking reading from the measuring cylinder. Also, filter paper was used instead of sintered glass crucible. Hence, the pore on filter paper might be bigger and allowed some excipients to pass through and impure ibuprofen was extracted. Other than that, the ibuprofen used was expired hence the active ingredient in it may degraded or spoiled. This may affects the amount of sodium hydroxide needed to neutralize the impure ibuprofen.

Those errors can be avoided by improving the steps of carrying out the experiment. As fine particle size of powder is a systemic error, repeating and averaging the results can minimize the deviation and get a more precise result. Parallax error can be eliminated by placing the eye at the position perpendicular to the scale on measuring cylinder or burette. Sintered glass crucible should be used to get the pure ibuprofen. New batch of ibuprofen should be used to eliminate the problem of expired active ingredient.

Conclusion :

0.3012g of ibuprofen active ingredient was obtained from the ibuprofen tablet. The content of active ingredient is not tally with the theoretical dosage expected. The percentage of deviation should be in the range of 85%-115% but the experimental value is 60.24%. The experiment should be repeated by using a new batch of ibuprofen to determine whether it fall in the range of 75%-125% so that the result is acceptable.

Question 5

5.      Explain the difference found in the procedure for dissolution test in United State Pharmacopoeia and the British Pharmacopoeia.

In dissolution test for capsule, it was stated in USP uses the rotating paddle from about one-third of its capsule products. The pharmacopoeias have attempted to overcome the problem of capsules floating by the use of a sinker and there are differences in those prescribed by the 3 major pharmacopoeias. The BP authorizes the use of one any product that floats and it has the most precise specification for one. It is constructed from an acid-resistant metal wire. The PhEur simply states that for products that float when using apparatus no.2, a glass or metal helix should be used to keep the dosage form horizontal at the bottom of the vessel. This sinker must be made from substances that are chemically inert in the media for it to be used in a dissolution test.

DOSAGE PERFORMANCE TESTS .

Title:                     Disintegration test for sugar-coated tablets.

Introduction:

For a drug to be absorbed from a solid dosage form after oral administration, it must first be in solution, and the first important step toward this condition is usually the break-up of the tablet; a process known as disintegration. The disintegration test is a measure of the time required under a given set of conditions for a group of tablets to disintegrate into particles which will pass through a 10 mesh screen. Generally, the test is useful as a quality assurance tool for conventional dosage forms. The disintegration test is carried out using the disintegration tester which consists of a basket rack holding 6 plastic tubes, open at the top and bottom, the bottom of the tube is covered by a 10-mesh screen. The basket is immersed in a bath of suitable liquid held at 37 o C, preferably in a 1L beaker. For compressed uncoated tablets, the testing fluid is usually water at 37 o C but some monographs direct that simulated gastric fluid be used. If one or two tablets fail to disintegrate, the test is repeated using 12 tablets. For most uncoated tablets, the BP requires that the tablets disintegrate in 15minutes (although it varies for some uncoated tablets) while for coated tablets, up to 2hours may be required 3 . The individual drug monographs specify the time disintegration must occur to meet the Pharmacopoeial standards.

Procedures:

1.       Apparatus for the disintegration test was set up.

2.       The temperature for the disintegration medium (water) was ensured at 37 ± 2°C.

3.       The time was set to 60 minutes. One tablet was introduced to each tube and the disk was added into each tube and the operation begins.

4.       At the end of the operation the tablet in each tube was checked.

Results

All the tablets disintegrate within 60 minutes.

Discussion

Disintegration test is widely used in the pharmaceutical industry for evaluation of disintegration capability of formulations (eg: tablets) and quality control of different dosage forms.

The disintegration test is performed to find out the time it takes for a solid oral dosage form like a tablet or capsule to completely disintegrate. The time of disintegration is a measure of the quality. This is because, for example, if the disintegration time is too high; it means that the tablet is too highly compressed or the capsule shell gelatin is not of pharmacopoeial quality or it may imply several other reasons. And also if the disintegration time is not uniform in a set of samples being analysed, it indicates batch inconsistency and lack of batch uniformity.

From the experiment, the time for tablets to disintegrate is about 19 minutes and 44 seconds. So, the time for disintegration of these tablets are low since it can disintegrate within the time given.

Conclusion

Disintegration process is important for the tablet to break-up after oral administration to release the active ingredient. Since the time taken for the tablet to disintegrate is 19 minutes 44 seconds, it means that the tablet has a good quality.

Title:

Dissolution test for tablets

Introduction:

Tablets or capsules taken orally remain one of the most effective means of treatment available. The effectiveness of such dosage forms relies on the drug dissolving in the fluids of the gastrointestinal tract prior to absorption into the systemic circulation. The rate of dissolution of the tablet or capsule is therefore crucial.

Dissolution is the process by which a solid solute enters a solution. In the pharmaceutical industry, it may be defined as the amount of drug substance that goes into solution per unit time under standardized conditions of liquid/solid interface, temperature and solvent composition. Dissolution is considered one of the most important quality control tests performed on pharmaceutical dosage forms and is now developing into a tool for predicting bioavailability, and in some cases, replacing clinical studies to determine bioequivalence. Dissolution behaviour of drugs has a significant effect on their pharmacological activity. In fact, a direct relationship between in vitro dissolution rate of many drugs and their bioavailability has been demonstrated and is generally referred to as in vitro-in vivo correlation, IVIVC.

Procedure:

1.       Each of the dissolution vessels was filled with the buffer solution up to 900 ml mark. The temperature was set to 37°C.

2.       The temperature of the dissolution medium was ensured it is at 37°C.

3.       One Ibuprofen tablet was placed into each dry basket assembly.

4.       The stirring speed was set to 150 rpm. The basket assembly was lowered into position in the vessel and the operation begins.

5.       After 30 minutes, 10 ml samples of dissolution medium were withdrew from each vessel for analysis and the solution was filtered using suitable filter. The sampling was done from a point half-way between the surface of the dissolution medium and the top of the rotating basket, and not less than 10 mm from the wall of the vessel. The volume of aliquot withdrawn for analysis was replaced with an equal volume of the same dissolution medium.

6.       A standard solution of ibuprofen was prepared by diluting 10.0 mg of ibuprofen reference standard to 50 ml with dissolution medium.

7.       2.0 ml of sample solution and 2.0 ml of standard solution were diluted with dissolution medium in separate volumetric flasks.

8.       The absorption of both solutions were measured in a 1 cm cell at a wavelength of 221 nm.

9.       The percentage amount of ibuprofen dissolved was calculated using the formula:

At/As × W/50 × 2/25 × P × 900 × 25/2 × 100/200

Where

At = absorbance of sample solution

 As = absorbance of the standard solution

 W = weight of ibuprofen reference standard used.

 P = purity of ibuprofen reference standard.

10.   From the results obtained, determine whether the tablets comply with the

requirements of the United States Pharmacopoeia.

USP limits: Not less than 75% of the stated amount of C13H18O2 dissolved in 30 minutes.

Results:

Absorbance of sample solution (At)	0.790
Absorbance of the standard solution (As)	3.612

At/As × W/50 × 2/25 × P × 900 × 25/2 × 100/200

= (0.790/3.612) x (10/50) x (2/55)x 0.98 x 900x (25/2) x (100/200)

= 9.74x10^-3 %

Discussion:

One of the most important factors to understand during drug development is the dosage form’s “bioavailability”.  This refers to the rate at which the drug product becomes available for absorption by the body.  The rate is governed by the time required for the drug product to dissolve in the gastrointestinal tract, and release the drug product contained in the tablet or capsule. 

Dissolution testing allows bioavailability to be measured, which is done using a tablet dissolution apparatus.  This system simulates the environment of the human gastrointestinal tract.  Samples are taken periodically through the study and assayed to measure drug product concentration.  A plot of the concentration over time of the study can be created that shows the rate of release of the drug substance from the dosage form.

As we know the limit in USP the percentage for dissolution is 75 % but for this experiment we only get 9.74x10^-3 %. This shows that the dissolution rate for this tablet very poor. This condition may be cause by several factors which are the tablet that we use already upon expiring date. Besides that it also may be caused by the error when test by using spectrometer due to lack of knowledge on how to use it.

Conclusion:

The dissolution percentage for this tablet is 9.74x10^-3 % which is not under the limit that had been fixed by USP.

UNIFORMITY OF WEIGHT OF TABLETS AND CAPSULES.

Objective:

To test the uniformity of weight of tablets and capsules whether it comply with the Pharmacopoeial standard or not.

Material and Apparatus:

Paralgin tablets, Ampillin capsules, weighing balance and weighing boats.

Method:

Tablets

1.       20 tablets are selected at random and weighed. The average weight is determined.

2.       Tablets are weighed individually and for each tablet, the percentage deviation of its weight from the average weight is determined.

3.       The deviation of individual weight from the average weight should not exceed the limits given below.

Average weight of tablet	Deviation (%)	Number of tablets
Less than 80 mg.	± 10.0 ± 20.0	Minimum 18 Maximum 2
80 mg to 250 mg	± 7.5 ± 15.0	Minimum 18 Maximum 2
More than 250 mg.	± 5.0 ± 10.0	Minimum 18 Maximum 2

Capsules

1.       20 capsules are selected at random.

2.    A capsule is weighed. The capsule is opened and the contents are removed as completely as possible. The emptied shells are weighed. The net weight of its contents is determined, that is by subtracting the weight of the shells from the weight of the intact capsule.

3.    The proceduresare repeated with other 19 capsules.

4.    The average net weight from the sum of the individual net weights is determined.

5.    The percentage deviation from the average net weight for each capsule is determined.The deviation of individual net weight should not exceed the limits given below:

Average net weight of capsule	Deviation (%)	Number of tablets
Less than 300 mg.	± 10.0 ± 20.0	Minimum 18 Maximum 2
300 mg or more	± 7.5 ± 15.0	Minimum 18 Maximum 2

Results and Calculation:

Formula

Tablets

Tablets	Weight (g)	Deviation (%)
Total	13.6449
Average	0.6822
1	0.6856	0.50
2	0.6881	0.86
3	0.6805	-0.25
4	0.6846	0.35
5	0.6781	-0.60
6	0.6657	-2.42
7	0.6638	-2.70
8	0.6675	-2.15
9	0.6832	0.14
10	0.6890	0.99
11	0.6954	1.93
12	0.6972	2.20
13	0.7000	2.61
14	0.6751	-1.04
15	0.6839	0.25
16	0.6921	1.45
17	0.6727	-1.39
18	0.6625	-2.89
19	0.6905	1.22
20	0.6894	1.06

Capsules

Capsules	Weight (g)			Deviation (%)
	Whole	Cap	Net
1	0.3607	0.0583	0.3024	3.53
2	0.3590	0.0632	0.2958	1.27
3	0.3702	0.0652	0.3050	4.42
4	0.3515	0.0651	0.2864	-1.95
5	0.3609	0.0627	0.2982	2.09
6	0.3477	0.0649	0.2828	-3.18
7	0.3659	0.0635	0.3024	3.53
8	0.3590	0.0609	0.2981	2.05
9	0.3554	0.0625	0.2929	0.27
10	0.3593	0.0632	0.2961	1.37
11	0.3578	0.0633	0.2945	0.82
12	0.3385	0.0622	0.2763	-5.41
13	0.3342	0.0618	0.2724	-6.74
14	0.3540	0.0630	0.2910	-0.38
15	0.3439	0.0631	0.2808	-3.87
16	0.3495	0.0672	0.2823	-3.36
17	0.3632	0.0574	0.3058	-4.69
18	0.3522	0.0624	0.2898	-0.79
19	0.3520	0.0592	0.2928	0.24
20	0.3584	0.0613	0.2971	1.71
Total			5.8429
Average			0.2921

Discussion:

                The tablets used is Paralgin(paracetamol500 mg)with average weight of 682 mg therefore, we used this rule:

More than 250 mg.

± 5.0 ± 10.0

Minimum 18 Maximum 2

It seems that all 20 tablets tested did not exceed.The positive deviation means that the individual weight is more than the average weight and negative percent deviation indicates individual weight is less than average weight.

                The capsules used in experiment is Ampicillin trihydrate (Ampicillin BP 250 mg) with average weight of 292 mg therefore, we used this rule:

Less than 300 mg.

± 10.0 ± 20.0

Minimum 18 Maximum 2

It seems that no capsule deviate more than  %.

Conclusion:

                All tablets and capsules tested comply with pharmacopoeial standard of uniformity of weight.

Question

Give reasons for the non-compliance to test for uniformity of weight.

The non-compliance to test for uniformity of weight is due to:

a.       The decayed/expired/degeneration/decomposed ingredient of the drug.

b.      Uneven feeding of granules into the die due toirregular movement of the lower punch that cause variation in capacity die space.

c.       Packing geometry.

References:

Gresham HS.http://science.halleyhosting.com/sci/soph/inquiry/percentdev.htm. Percent Deviation.Student Watershed Research Project.Retrieved on23rd December 2013.