Thursday 3 December 2015

Content of ibuprofen (assay)

Title
Content of ibuprofen (assay)

Aim
To determine the content of ibuprofen

Introduction
Ibuprofen is a painkiller, which is available over-the-counter, without a prescription. It is one of a group of painkillers called non-steroidal anti-inflammatory drugs (NSAIDs), and can be used to ease mild to moderate pain such as toothache, migraines and period pain, to control a fever which is in high temperature, also known as pyrexia, to ease pain and inflammation caused by rheumatic diseases and musculoskeletal disorders and to ease pain and swelling caused by sprains and strains, such as sports injuries.
Ibuprofen should be avoided by people with certain health conditions, such as a current or recent stomach ulcer, or a history of bad reactions to NSAIDs. It should be used with caution by older people, and people with certain health conditions, including asthma or kidney or liver problems.
Ibuprofen is made by many different companies, under many different brand names and in a wide range of forms, including tablets or caplets, gels, sprays and liquids. The dosage prescribed usually for adult and child over 12 years, initially 300-400mg, 3-4 times daily. The dosage will increased if necessary to maximum 2.4 g daily. The maintenance dose of 0.6-1.2g daily may be adequate. The dosage given of Ibuprofen to children who had pain and fever are different in age range. Usually Ibuprofen is marketed which 200 mg ibuprofen in a tablet. In oral suspension the content of ibuprofen is 100mg/5ml.

Figure 1: Structure of ibuprofen

Apparatus
Weighing boat, electronic balance, spatula, conical flask, beaker, dropper, measuring cylinder, filter funnel, filter paper, glass rod, hair dryer, burette, titration burette clamps.

Materials
20 tablets of Ibuprofen, 50 ml chloroform, 100 ml ethanol, phenolphthalein, 0.1 M sodium hydroxide.

Procedure
1. 20 Ibuprofen Tablets are weighed and powdered previously selected at random.
2. Quantity of powder containing 0.5 g ibuprofen is extracted with 20 ml chloroform for 15 minutes and filtered through a sintered glass crucible (BS Porosity No. 1).


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

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

Result and calculations
Observation: The solution turns from colourless to pink in titration.
Materials
Weight (g)
Powder of Ibuprofen + weighing boat
11.1400
Weighing boat
3.2000
Powder of Ibuprofen
7.9400

Weight of powder of 20 tablet Ibuprofen: 7.9400 g
1 tablet contain 200 mg Ibuprofen
20 tablet contains 20 x 200 mg Ibuprofen = 4000 mg = 4 g Ibuprofen
4 g Ibuprofen contains 7.9400 g of tablet powder
0.5 g Ibuprofen contains:

 0.50g/4.00gx/7.94g

x = 0.9925 g of powder contain 0.5 g Ibuprofen
Thus, 0.9925 g of tablet powder was weighed and dissolved with 20 ml chloroform.

NaOH + C13H18O2  C13H17ONa + H2O
Initial burette reading of 0.1 M NaOH = 30.0 ml
End point reading of 0.1 M NaOH = 50.1 ml
Volume of 0.1 M NaOH = 50.1 ml – 30 ml = 20.1 ml
No. of mole of NaOH used in titration =MV/1000
If 1 ml 0.1 M NaOH is equivalent 0.02063 g C13H18O2.
20.1 ml 0.1 M NaOH is equivalent to 0.02063 g x 20.1 ml = 0.4147 g C13H18O2.
Thus, the content of ibuprofen is 0.4147 g.

Discussion
Percentage of deviation = (experiment value-theoretical value)/ theoretical value x 100%
Theoretically, 0.9925 g of Ibuprofen tablet powder contains 0.5 g Ibuprofen
Percentage of deviation = (0.4147g-0.5g)/0.5g x 100% = 17.06%
     
      The percentage of deviation is not too large, which is 17.06%. This might be caused by some errors done during the experiment. Errors might be done during the powder of Ibuprofen tablets using mortar and pestle. Some powder might be displaced out of the mortar when too much force was applied when powdering the tablets which lead to decrease in mass of the total Ibuprofen powder which causes inaccurate results. Besides, error might be done when the process of filtration was not being conducted properly as filter paper of smaller size was used and the residue is not being filtrated completely before proceeding to the next step. Another error might occur when drying the filtrate. The filtrate might be over dried and the ibuprofen evaporated, causing the mass of ibuprofen decreased and leading to inaccurate results. Apart from this, error might be done during titration when the process was stopped and the reading of volume was obtained when the end-point was not being reached which leads to inaccurate volume of NaOH needed. Parallax errors might also occur throughout the experiment when the eye level was not perpendicular to the reading scale on the measuring cylinder while measuring the solution. Beside this, the Ibuprofen tablets used were expired, which might have reduced amount of Ibuprofen content.
To overcome the errors above, some precaution steps should be taken. Firstly, powdering of Ibuprofen tablets should be done carefully by applying force enough to powder the tablet but not causing the powder to spill out of the mortar. Besides, the filtration process should be carried out more properly by using filter paper of appropriate size and patiently wait until all residue being filtered. During drying of filtrate using a hot gun, drying should be stopped once the liquid being evaporated but not until the white residue which is the ibuprofen being evaporated. Apart from this, the titration should only be stopped when the end point which is when the solution turns pale pink, has reached. Parallax errors should be avoided by placing the eye level perpendicular to the reading scale on the measuring cylinder while measuring volumes of solutions. Besides, Ibuprofen tablets used must not be expired to obtain a more ideal results.

Conclusion
The percentage of deviation is 17.06% which means that the content of ibuprofen is 82.94% of the labeled content. Besides, the errors must be prevented to obtain more accurate results.


Reference



   


Dosage performance tests:Dissolution test for tablets

Title
Dosage performance tests:Dissolution test for tablets

Objective:
 i) To determine the percentage of the amount of ibuprofen dissolved in the dissolution medium at the wavelength of maximum
ii) To determine the amount of ibuprofen dissolved from UV absorbance at wavelength of 221nm in comparison with standard solution.

Introduction:
            Dissolution test is one of the in vitro tests usually employed to assess the quality of oral pharmaceutical solid dosage forms such as tablets and capsules. Dissolution test s can be used to guide formulation developments, identify critical manufacturing variables, monitor formulation quality from batch to batch, predict the in vivo performances and also serve as a surrogate for bioavailability and bioequivalence. However, the role of the dissolution test has been extended to measure the rate drug release from various other forms such as topical, and transdermal systems and suppositories.
            The tablet that has been used for this experiment is ibuprofen. The basket method is used and a single tablet is placed into the basket to allow dissolution to take place within 30 minutes. The sample is then diluted with dissolution medium (buffer) and tested using the spectrophotometer for the absorption of the wavelength of 221nm.
The percentage amount of ibuprofen dissolved is calculated using this formula:        

At/As x W/ 50 x 2/25 x P x 900 x25/2 x 100/200
where,
At = absorbance of the sample solution
As = absorbance of the standard solution
W = weight of ibuprofen reference standard used
P = purity of ibuprofen reference standard

Materials:
·         Ibuprofen tablets
·         Dissolution medium
·         Ibuprofen standard solution

Apparatus:
·         Dissolution tester
·         Spectrophotometer
·         Filter funnel
·         10ml measuring cylinder
·         Dropper
·         50ml volumetric flasks
·         Weighing boat
·         Electronic balance

 Procedure:
1. Each of the dissolution vessels is filled with the buffer solution to 900 ml mark. The temperature is set to 37oC.
2. The temperature of the dissolution medium is checked. It is ensured to be at 37 ± 0.5oC.
3. One Ibuprofen tablet is placed into each dry basket assembly.
4. The stirring speed is set to 150 rpm. The basket assembly is lowered into position in a vessel and the operation started.
5. After 30 minutes, 10 ml of the samples of the dissolution medium were withdrawn from each vessel for analysis and the solution was filtered using a suitable filter.
6. A standard solution of ibuprofen is prepared by diluting 10.0 mg of ibuprofen reference standard to 50 ml with dissolution medium.
7. 2.0 ml of the sample solution and 2.0 ml of the standard solution is diluted to 25 ml with dissolution medium in separate volumetric flasks.
8. The absorption of both solutions is measured in a 1 cm cell at a wavelength of 221 nm.

9. The spectrophotometer readings for both solutions were recorded. The percentage amount of ibuprofen dissolved was calculated by using the given formula.


10. From the results obtained, the tablets were determined whether it compiled with the requirements of the British Pharmacopoeia.

Results and calculations:
Type of solution
Spectrophotometer absorbance reading
Standard
1.783
Sample
0.849

Percentage amount of ibuprofen dissolved:
= 0.849/1.783 x 10/50 x 2/25 x 0.98 x 900 x 25/2 x 100/200
= 41.98 %

Discussion:
            Based on the results, the percentage amount of ibuprofen dissolved is 41.98%. Hence, we can conclude that the tablet did not comply with the requirements of British Pharmacopoeia.
            Several errors may have occurred when the experiment was being conducted in the lab. The tablet placed in the basket assembly may have been soaking in water for some time due to the starting trouble caused by the dissolution tester. This may have altered the composition of the ibuprofen tablet itself. Besides, the sample solution was not filtered properly using the filter as per guided by the lecturer, therefore, allowing some small undissolved ibuprofen tablets to be present in the volumetric flask. This would have affected the reading of the ibuprofen in the spectrophotometer as the amount of light absorbed is proportional to the concentration of solute present.
            Moreover, parallax error is prone to occur while measuring the solutions using the measuring cylinder and volumetric flask. The concentration of the solution would have been altered if incorrect amount of solution has been mixed together, thus resulting in the spectrophotometer to project wrong reading of absorption. This can prevented if the experimenter has made sure that his eyes are perpendicular to the plane of measuring cylinder and the to the calibration mark of the volumetric flask.

Questions:

4. Why is dissolution test suitable to be used for batch to batch quality control?
Dissolution test stimulates the availability of active substance and allows the prediction of the time for complete release of the material from the dosage form. As soon as the composition and the manufacturing process are defined, dissolution testing is used in the quality control of scale-up and of production batches to ensure both batch-to-batch consistency and that the dissolution profiles remain similar to those of pivotal clinical trial batches. 

5. Describe other apparatus that you can use to conduct dissolution test apart from the one found in the laboratory.
·         Dissolution apparatus 2- Paddle ( conducts dissolution testing for oral solid dosage forms, mainly tablets)
·         Dissolution apparatus 3- Reciprocating cylinder ( generally used for transdermal dosage forms)
·         Dissolution apparatus 4- Flow- through cell (to benefit from complete flexibility on media volumes and to reproducibly position dosage forms such as powders.  

Conclusion
 From the experiment, the tested ibuprofen is not complied with the British Pharmacopeia as only 41.98% of  the tablet is dissolved during the experiment.

Reference
·         Tablet dissolution testing
http://www.pharma-test.de/manual-tablet-dissolution-testing/
·         Dissolution
http://www.pharmacopeia.cn/v29240/usp29nf24s0_c711h.html
·        Dissolution testers (apparatus)
  http://www.erweka.com/products/category/dissolution-tester-usp-apparatus-1256.html?f=1