Experiment 4 Dosage Performance Tests

Objectives:
1. To study and evaluate the disintegration test for coated tablets

2. To study and evaluate the dissolution test for tablets.

Date of experiment: 12th December 2014

Introduction

       Before an oral route drug being absorb into the bloodstream via gastrointestinal (GI) tract, it has to undergo two processes - disintegration and dissolution. Disintegration is where capsules, tablets and granules are break up to powder particles to increase the surface area of the drug exposed to the gastrointestinal fluids, which is followed by absorption into the systemic circulation. A tablet that fails to disintegrate or disintegrates slowly will cause incomplete absorption or delay the onset of action of drug as the drug particle is too big to pass through the membrane of GI tract .

        Dissolution is define as the transfer of molecule and ions from a solid state into solution. It involves the relocation of a solute molecule (eg. drug molecule) from an environment which is surrounded by it’s own identical molecules. These molecules would forms intermolecular attractions with other non-identical molecules in the surrounding, and later depart from it’s  latter of  identical molecules. The size of the latter would decrease during dissolution. The small size drug molecules or particles that has undergone dissolution will be able to be absorbed into the GI membrane.

         Dissolution and disintegration process in tablets are critical and will determine it’s bioavailability and therapeutic activity. Thus in this experiment on dosage performance test is carried out to test the disintegration of film-coated tablets and dissolution of tablet available in the market and to evaluate that whether these tablets comply with the tests.

Experiment Method

A)Apparatus
Measuring cylinder 10ml, beaker 50ml, 10ml syringe, filter funnel, 50ml volumetric flask, glass rod

B) Materials:
Buffer solution, tap water, distilled water, Mefenamic acid B.P. 500mg film-coated tablets, Ibuprofen B.P. 200mg film-coated tablet, filter paper

C) Model of Analytical Equipments: Tablet disintegration machine, tablet dissolution tester, spectrophotometer

D)Procedures

i) Disintegration test for coated tablets

1. The apparatus for the disintegration test is set up according to it’s operation manual.

2. The temperature of the disintegration medium (water) is ensure at 37 ± 2°C.

3. The time is set to 60 minutes. One tablet is introduced into each tube, the disk is added into each tube and the operation is started.

4. The tablet in each tube is checked at the end of the operation.

5. Tablets comply with the test if all 6 tablets disintegrate in 60 minutes. If there is any

tablet that does not disintegrate, the test is repeated  using 6 new tablets but replacing the disintegration medium (water) with 0.1M hydrochloric acid. Tablets comply with the

test if all 6 tablets disintegrate in the acidic medium.

ii)Dissolution test for tablets

1. Each dissolution vessel is filled up with the buffer solution to 900 ml mark. The

temperature is set to 37°C.

2. The temperature of the dissolution medium is checked and ensure at 37 ± 0.5°C.

3. One Ibuprofen Tablet is placed into each dry basket assembly.

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

5. After 30 minutes, 10 ml samples of the dissolution medium is withdrawn from each

vessel for analysis and the solution is filtered using suitable filter.Sampling is 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 is replaced with an equal volume of same dissolution medium.

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 sample solution and 2.0 ml of standard solution are diluted to 25 ml with

dissolution medium in separate volumetric flasks.

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

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

A t /A s  × W/50 × 2/25 × P × 900 × 25/2 × 100/200

Where A t = absorbance of sample solution

A s = absorbance of the standard solution

W = weight of ibuprofen reference standard used.

P = purity of ibuprofen reference standard.

10. From the results obtained, the tablets are determined whether it comply with the

requirements of the United States Pharmacopoeia.

USP limits: Not less than 75% of the stated amount of C 13 H 18 O 2 dissolved in 30

minutes.

Result and Calculations

i) Disintegration test for coated tablets

All three Mefenamic acid B.P. 500mg film-coated tablets disintegrate in the disintegration medium (water) within 60 minutes. The tablets  are completely disintegrated in 9 minutes and 44 seconds.

ii) Dissolution test for tablets

	Absorption of solution (ABS)	K*ABS
Standard Solution of Ibuprofen	3.436	3.4362
Sample Solution of Ibuprofen	1.872	1.872

The percentage amount of ibuprofen dissolved

A t /A s  × W/50 × 2/25 × P × 900 × 25/2 × 100/200

A_t = 1.872                          A_S= 3.436
W=10mg                    P= 0.98

                                                                                                 

Discussions

        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. The machine used in this test is the tablet disintegration machine. The disintegration medium is set around 37°C to mimic the temperature of human body. The up and down movement of the basket in the machine will mimic the agitation of gastric content when the tablet is inside the GI tract of human body.
         In this experiment, the Mefenamic acid 500mg B.P. film coated tablets managed to disintegrate less than 60 minutes. All the tablets disintegrate in 9 minutes 44 seconds. The Mefenamic acid tablets has passed the criteria of disintegration test. Film-coated tablets are compressed tablets coated with a thin layer of  polymer. This produces a skinlike film on the tablet. The polymer has expanded film and will allow the penetration of water into the tablets which induces relatively rapid disintegration. 

        Dissolution testing is a critical preformulation solubility analysis research tool in the process of drug discovery.  This test measure the stability of the investigational product, achieving uniformity in production lots and determining its in vivo availability. From the dissolution test, it was found that the percentage of ibuprofen tablets dissolved is 48.05%. This is less than the U.S Pharmacopoiea limits, where not less than 75% of the stated amount of ibuprofen dissolved in 30 minutes. These tablets has failed it’s test. It  could be due to various factors such as errors in formulation and chemical and physical properties of the solid oral dosage forms. 

           A few errors has occurred during the experiment. Firstly, the eye level is not maintain perpendicular with the measuring scales of the apparatus. The eye level is also not in the same level with the meniscus while measuring the amount of solutions. This could cause parallax error and will affect the results. Besides that, while taking sample from the dissolution medium with a syringe, air bubbles are formed inside the syringe. The air bubble will displace some amount of the liquid in the syringe.  This will reduce the amount of sample solution required to be taken and affect the result. During spectrophotometric assay, same dropper is used while placing a small amount of standard solution and sample solution into the cuvette. The dropper may not be cleaned properly before applying with another solution. This would alter the concentration of the active ingredient in the solution and affect the result.

         To overcome these problems, a few precautions are taken. Firstly make sure eye level is perpendicular to the measuring scale and same level with the meniscus to prevent parallax error. While taking sample solution with syringe, make sure no air bubble is formed. If air bubble is formed, tap the syringe lightly till the air bubbles floats onto the surface and burst. Make sure the dropper is cleaned thoroughly with buffer solution before applying the sample or standard solution onto the cuvette.

Conclusion:

Disintegration and dissolution test is important to determine the quality and efficacy of the solid dosage forms including the bioavailability of solid dosage forms. 

Appendix:

Disintegration Test for coated Tablets

                                                    
                                                                           Figure  (a)      
                                                   
                                                                          Figure  (b)

                                                    
                                                                         Figure  (c)  
                                         

                                                                             Figure  (d)

Figure (a), (b), (c) : Container of   film-coated Mefenamic Acid tablets
Figure (d) :  Mefenamic Acid tablets
Tablets used: Mefenamic Acid B.P. 500 mg. film-coated tablets
Indications:
Mild to moderate pain in muscular aches and sprains; rheumatoid arthritis, osteoathritis and related conditions; and dysmenorrhoea
Manufactured by: Asia Pharmaceutical Products Sdn. Bhd.


                                          
                                                                     Figure (e)

                                 
                                                                    Figure (f)
Model of Analytical Equipment Used: Tablet dissolution machine (shown in figure (e) and (f) )

Dissolution test for Tablets:

                                  
                                                                        Figure (g)
Figure (e): Blister pack of Ibuprofen tablets

Tablet used: Ibuprofen B.P. Film-coated B.P. 200mg tablet
Indications: For symptomatic treatment of rheumatoid arthritis, juvenile rheumatoid arthritis and osteoarthriti; mild to moderate pain; dysmenorrhea; reduce fever. 
Manufactured by: Royce Pharma Manufacturing Sdn. Bhd.

                                           
                                                                       Figure (h)     
                                     
                                                                        Figure (i)
                                               
                                                                       Figure (j)
Model of Analytical Equipment used: Tablet dissolution tester (as shown in figure (h) (i) (j)) , spectrophotometer