SUPPOSITORY

Title: Evaluation on the effect of different formulation on the characteristic of suppository.

Objective: To study the effect of different composition of base on the physical characteristic of suppositories.

 Introduction:

Suppository is a solid formulation that has different size and appearance and thus is suitable to be administered by rectal route. A good suppository must be melt after being administered into the rectum and release the drug content to achieve local or systemic effect. The drug must be spread in a suitable base of suppository. A good base should be nontoxic, nonirritate, no reaction with the drug and easily to be formed as a suppository. Different composition of base will influence the rate and limit of drug release from the suppository. In this experiment, the effects of the different base composition to the suppository physical characteristics and also to the drug release characteristics are evaluated.

Apparatus:                                                                

Analytical balance

Weighing boats

Spatula

50ml and 100ml beakers

Hotplate

5ml measuring cylinder

Suppository mould set

Water bath 37^oC

Dialysis bag

Thread

Glass rod

5ml pipette and pipette bulb

Plastic cuvette

UV spectrophotometer

Materials:

Polyethylene glycol (PEG) 1000

Polyethylene glycol (PEG) 6000

Paracetamol

Distilled water

Liquid paraffin

Procedure:

1. Paracetamol saturated stock solution is prepared by adding 10g of Paracetamol in 5ml distilled water.
2. The 10g suppository is prepared using the formulation below:

Suppository	Group	PEG 1000 (g)	PEG 6000 (g)	Paracetamol stock solution (ml)	Total (g)
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	0	9	1	10

3. The suppository is shaped using the suppository mould. The shape, texture and color of the suppository is observed and discussed.

4. The suppository is placed in the water bath 10ml at 37^oC and the time for the suppository to melt is recorded.

5. The suppository is placed inside the dialysis bag and placed in the 50ml beaker. The beaker then placed inside the water bath 37^oC.

6. The sample is pipette in 5 minutes interval and the release of the Paracetamol from the suppository is determined using the spectrometer UV/Vis. The distilled water must be stirred first before the sample is taken.

Results and Discussions:

1.      Compare the physical appearance of suppositories that are formed and discuss.

Aspects	Group 1	Group 2	Group 3	Group 4	Group 5	Group 6	Group 7	Group 8
Shape	Torpedo	Torpedo	Torpedo	Torpedo	Torpedo	Torpedo	Torpedo	Torpedo
Texture	Smooth, hard, oily	Smooth, hard	Smooth, hard	Smooth, hard, oily	Smooth, hard, oily	Smooth, hard	Smooth, hard, sticky	Smooth, hard
Colour	Even white	Even white	Uneven white	Uneven white	Even white	Even white	Milky white	Uneven white

In this experiment, all the suppositories formulated have the shape of a bullet or bullet-shaped since the mould that is being used is of this shape. The quantities of PEG 1000 and PEG 6000 are different for each group and this will lead to formation of suppositories with different physical characteristics.

2.      Plot a graph of the time needed to melt the suppository vs. the amount of PEG 6000 in the formulation. Compare and explain the results.

Content of PEG 6000 (g)	0		3		6		9
Group	1	5	2	6	3	7	4	8
Time (min)	31	54	27	30	40	50	73	65
Average time (min) (x + SD)	(42.5 + 11.5)		(28.5 + 1.5)		(45 + 5.0)		(69 + 4.0)

Based on the graph shown, we can observe that the time taken for the suppository to melt is not directly proportional to the PEG 6000 content in gram. The function of the PEG 6000 content is as a suppository base. As the general knowledge, increasing the mass of the PEG 6000 will make the suppository more solid. For that, the time taken for the suppository to melt will be longer as the mass of the PEG 6000 increase. As shown on the graph above, the time taken for the suppository to melt which content 9g of PEG 6000 is 65 minutes which the longest time among the result. While the shortest time taken for the suppository to melt is the suppository that contain 3g of PEG 6000 which is 28.5 minutes.

Theoretically, the time taken for the lowest amount of PEG 6000 should be lowest and vice versa but the results we obtained is totally inappropriate. The deviation of the result from the story is majorly effected by the errors occur while conduct the experiment. Defect of suppository made reduction in mass and will reduce the time for suppository to dissolve. Error made during measured, and transferred of the ingredient during making of suppository also may alter the result. There also possibility that suppository does not solid enough when we taken out from the refrigerator. The unsolidified suppository made it easier to be dissolved in water bath. The heating process using water bath also may produce this result. Some of the group might stir the beaker containing suppository which make it faster to dissolve.

3.      Plot a graph of UV absorption against time and give explanation.

Time (min)	UV absorption
	0	5	10	15	20	25	30	35	40
UV absorption at 520nm	0.204	0.206	0.133	0.132	0.053	0.048	0.048	0.047	0.042

Time (min)	UV absorption
	45	50	55	60
UV absorption at 520nm	0.118	0.048	0.054	0.050

The aim of this experiment is to measure the amount of drug that can be released from the suppository into the blood circulation based on its amount of ingredients that made up of PEG 1000, PEG 6000 and paracetamol stock solution. To provide a temperature that is same with the human body temperature, the dialyses beg is immersed in 37 0 C of water in order. The dialyses beg represents the phospholipids membrane while the solution in the beaker represents the blood plasma. The value of UV absorption is correspond to the amount of paracetamol release from the suppository in the dialysis beg into the surrounding solution in the beaker.

            For 10g of suppository II, the compositions are made up 1g of paracetamol stock solution, 3g of PEG 6000, and 6g of PEG 1000. The amount of PEG 1000 is the higher than suppository III and IV but lower than suppository I. Polyethylene glycol is a non-ionic polyhydroxyl compound.  Different molecular weights have different solubility, surface tension, viscosity, freezing point and melting points.  PEG tends not to interact with biological chemicals. PEG 6000 responsible to the release of drug in the slow manner. 

            Based on the graph of UV absorption in 520nm versus time shown above, generally the mode of UV absorption decreases by time where on the beginning of the experiment, the results show that the UV absorption is 0.204 and it decreases by time until 0.05 after one hour. However, the amounts of UV absorption should be increases with time theoretically. The graph also shows fluctuation in the mode of UV absorption. After first 5 minutes, the amount of UV absorption increases slightly to 0.206 and it drops drastically to 0.133 after 10 minutes. After 20 minutes, the amount of UV absorption continues to decrease from the previous reading to 0.053. The graph only shows increases in absorption after 45 minutes with a significant increase to 0.118 but drops again to 0.048 after 50 minutes. The absorption then increases to 0.054 but again decreases to 0.050.

     The errors and fluctuation in the reading obtained may due to some errors occur while handling the sample solution and curvet. There may be some impurities and suppository residual left on the outer surface of dialysis beg during the experiment. Besides, some impurities from the suppository residual may have been introduced into the curvet while pipette the sample solution from the beaker and contaminated the sample. Besides that, some distilled water from the curvet may mixed with the sample in curvet if the it is not fully dried after being rinsed with distilled water and the outer wall of the cuvettes may not clean well with tissue before it is inserted into the UV spectrometer. This will then causes inconsistent increase in the UV absorption. Furthermore, the errors in this experiment may also due to the physical characteristic of the suppository as it show less homogenous, which means that the distribution of paracetamol is uneven.

4.      Plot a graph of UV absorption vs. time for other suppositories that have different formulation. Compare and discuss the results.

Graph of UV Absorption against Time for the Suppository Formulation with Different Compositions

Based on the graph above, suppository formulations with different compositions have different effect on drug release rate over time. In this experiment, the concentration of PEG 1000 and PEG 6000 are different in each suppository formulation. From the graph above, the value obtained has been inaccurate because suppository II has the highest drug release, which is measured in the UV absorption readings. According to theory, among the four suppositories, suppository I should have the highest drug release, which is measured in the UV absorption. This is because suppository I has the highest amount of PEG 1000. The hardness of the polyethylene glycol will increase with increasing molecular weight. When the hardness of the suppository increases, longer time will be needed to dissolve the drug and release the drug through the dialysis tube membrane. However, the graph above shows that suppository IV has the lowest drug release over time as well as the UV absorption, which is accurate according to the theory. This is because concentration of PEG 6000 is the highest in suppository IV, which means that the suppository IV is the hardest suppository and most difficult to dissolve among the four suppositories. According to the graph above, suppository III has intermediate UV absorption and the rate of drug release over time. Suppository III has higher UV absorption and drug release rate than suppository IV. This is because suppository III has the addition of PEG 1000 and lower amount of PEG 6000 than suppository IV. Thus, suppository III is softer than suppository IV and needs shorter time for the drug to dissolve and release through the dialysis tube membrane. The inaccuracy of the readings obtained occurs due to several errors, such as presence of impurities in the formed suppositories and improper method of compounding and preparation of suppository. Errors such as inaccuracy of the UV spectrometer and inconsistency in temperature during mixing of PEG 1000 and PEG 6000 may affect the rate of drug release from the suppository.

5.      What is the function of every substance used in this suppository preparation? How can the different contents of PEG 1000 and PEG 6000 affect the physical characteristics of the formulation of a suppository and the rate of release of drug from it?

PEG 1000 and PEG 6000 are polyethylene glycols which are polymers of ethylene oxide and water and the numerical indicates the molecular weight of the substance.  They act as water-miscible base carrier for active ingredient. Paracetamol is the active ingredient in this experiment.

The different amount of PEG 1000 and PEG 6000 used can influence the physical characteristic and the release rate of drug from suppository base. Higher amount of PEG 6000 increase hardness of suppository formed due to stronger hydrogen bond formed between molecules. Due to this strong hydrogen bonding, the drug release rate will be lowered. Using higher amount of PEG 1000 will result in softer suppository. This is due to weaker hydrogen bond formed between the molecules. Lipophilicity of PEG 1000 is higher thus result in greasier suppository. Drug release will be faster because the bond formed is weaker.

            Different characteristic of suppositories can be formed by varying amount and molecular weight of PEG used. Therefore by varying the combinations of PEG, we can obtain desired consistency and characteristic of suppositories. A balance of lipophilicity and hydrophilicity of suppository base can be achieved by this combination. Thus, bases that fulfill desired characteristics can be used in formulation and this will lead desired rate release of drug from the suppository base.

Conclusion:

Different percentage of combination of PEG 1000 and PEG 6000 affects the physical characteristics of the suppository and the rate of release of the active ingredient.

References:

1.       https://www.inkling.com/read/ansel-pharmaceutical-dosage-form-drug-delivery-9th/chapter-12/suppository-bases

2.       http://pharmlabs.unc.edu/labs/suppository/bases.htm