SUPPOSITORY

TITTLE : TEST ON THE EFFECT OF DIFFERENT CONTENTS ON THE 

CHARACTERISTICS OF SUPPOSITORY FORMULATION.

Introduction

Suppository is a solid formulation with various sizes and shape suitable for rectal administration. A good suppository should melt after administration into the rectum and release drugs for local or systemic effect.

The drugs should be distributed in a suitable suppository base. A good base should be non-toxic, no irritation, no reaction with the drug and easy to be form into a suppository. A different base composition will influence the rate and limit of drug release from the suppository.

In this experiment, the effect of different base composition to the physical characteristic of formed suppository and the effect of drug release will be studied.

Apparatus

Weighing scale

1 weighing boat

Spatula

1 beaker (50ml) and 1 beaker (100ml)

Hotplate

1 measuring cylinder (5ml)

1 set of suppository mould

Water bath (37°C)

1 dialysis bag (10cm)

2 threads

1 glass rod

1 pipette (5ml) and pipette bulb

1 plastic covet

Spectrophotometer UV/Vis

Materials

Polyethylene glycol (PEG) 1000

Polyethylene glycol (PEG) 6000

Paracetamol 

Procedure

     1.       A concentrated solution of paracetamol was prepared (10 g on 5 ml of distilled water).  

     2.       A paracetamol suppository (10g) was prepared using the formula.

     1.       The suppository was formed using the suppository-mould. The shape, texture and the colour of the suppository were compared.

     2.       One suppository was inserted into a beaker containing distilled water (10 ml, 37°C) and the time taken for the suppository to melt was recorded.

     3.       One suppository was placed into a dialysis bag and both ends of the bag were tied. The bag was placed into a beaker (100ml) containing distilled water (50ml) which has been heated to 37°C.

    4.       At each interval of 5 minutes, an aliquot sample (3-4ml) was pipette and the release of paracetamol from the suppository was determined using the spectrometer UV-visible. The distilled water was stirred before the sample is taken.

RESULTS AND DISCUSSIONS

      Compare the physical appearance of the suppositories and give explanation

            The different quantities of Polyethylene Glycol (PEG) which are PEG 1000 and PEG 6000 for each base formulation of suppositories will produce different physical characteristics of those suppositories. Based on the experiment, all the suppositories have the shape of a bullet since the mould that is being used is of this shape.

            For the formulation that has the highest amount of PEG 1000, which means that it has the lowest quantity of PEG 6000 shows greasy surface compared to the other suppositories. In other words, the higher the quantity of PEG 6000 in a formulation, the less greasy the suppository will be. Besides, all the formulation of suppositories has smooth texture. As for the hardness, all the suppositories produced are hard. Theoretically, the higher amount of PEG 1000 compared to PEG 6000 will give softer suppository and vice versa. The inaccurate result may due to some errors occurred throughout the experiment. The softer suppository provides ease to be administered to the patient compared to the hard one and it may lead to pain in the process of administering. Besides, it will easily melting within the body and also dissolves in body fluids.   

             For the colour of suppositories, since the active ingredient that we used is paracetamol which is white in colour, the colour of the suppositories produced also white but differ in the transparency degree. The colour changes from evenly white to uneven white with decreasing PEG 1000. This means that the formulation with the lower amount of PEG 1000 is more transparent compared to the others. 

2. Plot a graph of time needed to melt suppository against the content of PEG 6000 in the formulation. Compare and discuss the result.

Based on the graph, 9g PEG 6000 melts the longest followed by 6g, 0g and 3g. Theoretically, less PEG 6000 will melts first. In this experiment, 0g is not the fastest to melt instead, 3g is. Therefore, there may be some mistake occurred and as we are group 1, we will discuss about our experiment only. During experiment, the temperature of water bath is not constantly at 37°C because there are many other groups using the same water bath hence the temperature of water inside beaker may be lower than 37°C. The deviation between our group and group 5 is considered big that is 8.1 and their group melts at 54 minutes. This may be due to the cooling of suppository in freezer take too long hence the suppository freezes and take time to defrost before melts.

3.       Plot a graph of UV absorption against time. Give explanations.

From the graph obtained above, the UV absorption at 520nm is the highest during 10 minute. The UV absorption at 520nm is in an increasing order except there is slightly drop during the 25 minute and 60 minute. Theoritically the longer the period the dialysis bag stays in the solution, the more the amount of paracetamol diffuses out of it, and hence the higher the value of UV absorption because more UV light is absorbed. In this experiment, dialysis bag resembles the lipid bilayer membrane while the distilled water simulates the human plasma which represents the drug diffussion mechanism in our body. At 37 ^oC, the drug in the suppositories will diffuse into the systemic circulation due to the concentration gradient between the melted suppositories in the dialysis bag and dilutes solution outside the dialysis bag. This may due to some error in handling the sample and inapproriately use of machine. Other reason may be impurities in the sample container due to incomplete washing.

4.  Plot a graph of UV light absorption against time for the suppository formulation which contained different compositions. Give explanation.

Mean:

I=0.098

II=0.075

III=0.027

IV=0.020

From the graph above, the suppository I has the highest UV absorption at 520nm, which means it has the highest concentration of paracetamol in the distilled water, followed by formulation II, III and IV.  The results are tally to the theoretical value because different formulations of suppository give rise to different rate of drug release profile. The releasing rate of paracetomol is measured by spectrometry. Theoretically, the greater amount of PEG 6000, the slower the drug will be released from suppository. This is because the higher amount of hydrogen bonds formed between the base molecules and the paracetamol molecules hence the drug molecules (paracetamol), to be held stronger in the formulation and thus exert a lower releasing rate. Although the graph obtained from this experiment is very fluctuated, however generally there showed an increased concentration of paracetamol over time and the rate of drug releasing decreased with increased amount of PEG 6000 in each formulation. The graph obtained should be increasing initially and then become constant gradually as all the drug is released into the water..

          The fluctuation of the graph may be due to several errors occurred while handing the UV spectrometry or human errors, such as the incorrect way in the suppositories preparation or the presence of impurities in the formed suppositories. Besides, the uneven stirring process before the content of the mixture is pipetted also can contribute to the inaccuracy of the results which forming a few small fluctuations in the line graph. Some precaution steps should be carried out to obtain an accurate result. The surface of dialysis bag should be cleaned before immersing it into the distilled water and suppository should be filled into the bag carefully to prevent breakage of the bag.

5. What is the function of each ingredient that is used in the preparation of these suppositories? How does the usage of different content of PEG 1000 and PEG 6000 affect the physical properties of suppository formulation and rate of releasing of drug from it?

Paracetamol is active ingredient in the suppositories. Paracetamol is used as analgesic and antipyretic. It appears as white, odourless and light powder. PEG 1000 and PEG 6000 are the bases for the active ingredient, paracetamol of the suppository. They allow a smoother drug delivery of the suppository into the rectal. They also allow the absorption of paracetamol by the membrane to occur. A suitable combination of PEG allows an optimum drug releasing to occur, in which the drug will not be held strongly in the base and can be easily released. This is important to allow an optimum drug bioavailability to take place as the drug can be absorbed by mucosa membrane of the rectal.

The physical characteristic and the rate release of the suppository preparation can be interfered by the different combination of PEG1000 and PEG6000. As the proportion of PEG6000 increases, the drug becomes more difficult to be released from the suppository. Besides, the suppository also will become hard, crystal like and with a clear white colour. Proper combination of base should be determined to achieve a balance between hydrophilic and lipophilic characteristics.

CONCLUSION

From the experiment, we can conclude that the higher the amount of PEG 6000 in the formulation of suppository, the lower the rate of drug released.