SUPPOSITORY

Title
Assessment on the Impact of Different Ingredients on the Characteristics of a Suppository Formulations

 Date
19th May 2015
Objectives
To evaluate the effects of the different base composition to the suppository physical characteristics and also to the drug release characteristics

 Introduction

Suppositories are medicated, solid bodies of various sizes and shapes suitable for introduction into body cavities. The medicament is incorporated into a base such as cocoa butter which melts at body temperature, or into one such as glycerinated gelatin or PEG which slowly dissolves in the mucous secretions. Suppositories are suited particularly for producing local action, but may also be used to produce a systemic effect or to exert a mechanical effect to facilitate emptying the lower bowel.
The ideal suppositories base should be nontoxic, nonirritating, inert, compatible with medicaments, and easily formed by compression or molding. It should also dissolve or disintegrate in the presence of mucous secretions or melt at body temperature to allow for the release of the medications. As with the ointment bases, suppository bases composition plays an important role in both the rate and extent release of medications.

Apparatus

Analytical balance
Weighing boat
Spatula
50ml beaker
100ml beaker
Hotplate
5ml measuring cylinder
Suppository mould
Water bath (37°C)
Dialysis bag (10cm)
2 pieces thread
Glass rod
5ml pipette and pipette pump
Cuvette
Spectrophotometer UV/Vis

Materials

Polyethylene glycol (PEG) 1000
Polyethylene glycol (PEG) 6000
Paracetamol

Procedures
  1. Paracetamol stock solution is prepared (10g in 5ml of distilled water).
  2. Paracetamol suppositories of 10g are prepared using the formula as below:                                 
          Suppository
       Group
         Ingredient (g)
         Paracetamol Stock Solution (g)
       Total (g)
        PEG 1000
          PEG 6000
       I
          1,5,9
         9
         0
         1
      10
       II
          2,6,10
         6
         3
         1
      10
       III
          3,7,11
         3
         6
         1
      10
       IV
          4,8,12
         0
         9
         1
      10
                                  
  3. The suppositories are formed using the prepared suppository-mould.  The size, texture and colour of the suppositories formed are described and compared.
  4. A suppository is put into a beaker of distilled water (10ml, 37oC) and the time for it to melt is recorded.
  5. Another suppository is put into a dialysis bag and both the ends are tied properly.  The bag is then put into a beaker(100ml) containing distilled water(50ml) which is heated to a temperature of 37oC.
  6. An aliquot sample (3-4ml) is pipetted at every alternate 5 minutes and the release of paracetamol from suppository is determined using spectrometer UV-visible.  Make sure that the distilled water is stirred with glass rod before taking out the sample.

Discussion


Question 1
Compare the physical characteristics of suppositories that formulated and give comments.

                                     

Suppository
Group
Material(g)
Shape
Texture
Hardness
Colour
PEG1000
PEG6000
I
1
9
0
Bullet-shaped
Very Greasy
Soft
White
II
2
6
3
Bullet-shaped
Greasy
Slightly Hard
White
III
3
3
6
Bullet-shaped
Slightly Greasy
Hard
White
IV
4
0
9
Bullet-shaped
Least Greasy
Very Hard
Transparent

In this experiment, there are four characteristics of suppositories that will be observed based on different amount of PEG1000 and PEG6000 for each group. All the suppositories have the same shape which is bullet-shaped same like the shape of the mould being used. Based on the observation, the higher the PEG1000, the greasiest and the softest is the surface of suppository, while the higher the PEG6000, the hardest will the suppository be. As for the colour of the suppositories, the higher the PEG6000, the higher the transparency of the suppository. The others suppository become white because the active ingredient chosen is paracetamol, which is white in colour. Based on the comparison, the amount of PEG1000 and PEG6000 can determine the physical properties of suppositories. Thus, to prepare an ideal suppositories, the amount of PEG1000 and PEG6000 should be considered so that the physical characteristics are the best and ideal suppository.

Question 2
Plot a graph on time required for a suppository to melt against amount of PEG 6000 in the formulation. Compare and discuss the results.


Stated above is the graph on the time required for a suppository to melt against amount of PEG 6000 in the formulation. PEG 6000 is a water soluble base of suppository. Theoretically, the time taken for the suppository to melt should be decrease in the increasing amount of PEG 6000 in the formulation because it will give the solubility properties to the suppository. Based on the experimental data, the results do follow the theory but for the suppository which contains 9g of PEG 6000 requires slightly longer time than the one contains 6g of PEG 6000. The result for the particular suppository should be lower because it contains the highest amount of PEG 6000 which is most soluble in water. This problem may due to some experimental errors done by the group such as the mistakes in measuring the amount of PEG 6000 and the mistakes in taking the time required for the suppository to completely melt in the water. Although, the temperature of water being used by the group may be different from others. The temperature of water should be constant for every group throughout the experiment.

 Question 3
Plot graph UV absorption against time. Give explanation.


From the graph above, at the time 0min, less UV absorption measured. This is because, the suppository not start to dissolved yet. After 5 min, UV absorption increase that’s mean the suppository start to dissolve in distilled water. There are rapid increase of UV absorption at 10 min, this shows that the suppository start to dissolved eventually. At time 15-20 min, UV absorption reading start to decrease. There is some error during the experiment. The cuvette is not clean enough and the solution in the beaker, does not mix well during taking out the sample into the cuvette. After 20 minutes, the reading of UV absorption is constant. It shows that, the suppository do not dissolve anymore after 20 minutes.

Question 4
Plot graph of UV absorption against time for the suppository formulation with different compositions. Discuss and compare the results. 



Ultraviolet spectrometer is referred to absorption spectroscopy or reflectance spectroscopy in the ultraviolet-visible spectral region. It allows particle size distributions to be measured in concentrated systems without dilution. A light with certain wavelength is passed through the sample. When light travels through the sample, it loses energy which is also known as attenuated. If the sample contains the suspended particles, the attenuation of light will change due to a variety of scattering and absorption patterns. As a result, the size distributions of the particles in the sample are indicated as the measurement of the changes of energy of the light.
Dialysis tubing is used in this experiment. As it is semi-permeable, it only allows certain molecules to pass through by diffusion and some molecules such as polar compound are blocked to pass through the membrane. In the experiment, the dialysis tubing is used to determine the ability of the paracetamol of suppository to pass through the membrane and enter into the distilled water which is heated under 37 degree Celsius. It indicates the human’s biological barrier. Then, the amount of the content that passed through the dialysis tube is measured by using the ultraviolet spectrophotometer. Based on the results, the UV absorption at 524 nm is increasing with time for each of the suppositories. This shows that there is an increase in the numbers of particles of the suppositories diffused through the dialysis tube membrane.
From the graph above, it can be seen that suppository I has the highest UV absorption among the four suppositories because it has the highest amount of the PEG 1000 and it is the softest. Theoretically, the hardness of the polyethylene glycol will increase with increasing molecular weight. So, the softest suppository only require the shortest time to dissolve the drug and passing through the dialysis tube membrane. As the polyethylene glycol with molecular weight from 600 to 1000 is present in the semisolid form, it can pass through the dialysis membrane. Therefore, suppository I has the highest UV absorption as higher content of drug has passed through the dialysis membrane.
High proportion of high polyethylene glycol with larger molecular weight will produce harder suppository which release drug slowly and also brittle. Theoretically, suppository IV is the hardest suppository because it has the highest proportion of PEG 6000 which will produce the hard suppository that difficult to dissolve through dialysis membrane. However, the result shows that suppository II has the lowest UV absorption. This may due to some error occurred when conducting the experiment such as leakage occurred when transferring the sample by using dropper to measure dispersion of drug using spectrometer.
In conclusion, polyethylene glycol with high molecular weight should be mixing with medium or low molecular weight to produce a less brittle suppository with an optimal rate of drug release.
Question 5
What is the function of every material used in the preparation of this suppository?  How the different amount of PEG 1000 and PEG 6000 influence the physical properties of the formulation of the suppository and the rate of release of drug from it?

Paracetamol is the active ingredient in this formulation.  PEG 1000 and PEG 6000 means the polyethylene glycol have different molecular weight.  It acts as bases in this formulation.  Different amount of PEG 1000 and PEG 600 can influence the physical properties of the suppository and the rate of release of drug from it.  PEG 6000 has higher molecular weight compared to PEG 1000.  PEG that has higher molecular weight has the ability to withstand the temperature and more difficult to melt.  Thus, PEG 6000 has higher melting point compared to PEG 1000.  Therefore, the suppositories made from higher proportion of PEG 6000 will take a longer time to melt compared to the suppositories made from higher proportion of PEG 1000.  The release of drug from the suppository does not depends on the melting point.  This is because the higher the melting point, the longer the time taken for the drug to solubilize.  Thus, suppositories with higher amount of PEG 6000 will take a longer time to release the drug compared to the suppositories with higher amount of PEG 1000 where it can release the drug at a faster rate.

Conclusion
In the conclusion, the amount of polyethylene glycol with different molecular weight added into the suppository formulation will affect the hardness of suppository. The polyethylene glycol with smaller molecular weight produces a soft suppository while polyethylene glycol with larger molecular weight produces a hard suppository. To produce a less brittle suppository with optimal rate of drug release, polyethylene glycol with larger molecular weight should be mixed with those with smaller molecular weight.
References

pharmlabs.unc.edu/labs/suppository/bases.htm
http://www.ncbi.nlm.nih.gov/pubmed/2673303

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