SUPPOSITORY PART II

Conclusion:

Different composition of base can affect the physical characteristic of suppositories. High amount of PEG 6000 will produce hard and less greasy suppository. However, high amount of PEG 1000 will give soft and greasier suppository. Proper combination of PEG will give the optimum drug released rate.

 

References:

1. Pharmaceutical Practical. (1996). Diana M. Collett, Michael. E. Aulton.Churchill Livingstone.

2. Phsicochemical properties of pharmacy, Florence& Attwood, 3rd Edition.

3. David Troy. 2000. Remington: The Science and Practice of Pharmacy. Lippincott  Williams & Wilkins. 21th edition. Page 1079-1080

4. http://www.arpc.ir/Portals/0/Pdf/Products/Chemical/PEGChemicalGrade.pdf

5. http://www.arpc.ir/Portals/0/Pdf/Products/Chemical/PEGChemicalGrade.pdf

 

Appendix:

 

 

PRACTICAL 4: SUPPOSITORY

FACULTY OF PHRMACY

TECHNOLOGY PHARMACEUTICAL II

NFNF 2263

LABORATORY REPORT

PRACTICAL 4: SUPPOSITORY

 GROUP B4

LECTURER'S NAME :

 DR. NG SHIOW FERN

 

GROUP MEMBERS:

1.    LEE LI SHAN A136251

2.    YIP LEE ANN A136282

3.    MUHAMMAD SHAHIR BIN ABU BAKAR A136436

4.    AINAA ZURIANI BINTI ABDUL AZIZ A136650

5.    NOOR FARAHIN BINTI ARIFFIN A136602

 

 

 

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.

Group	Paracetamol Stock Solution (ml)	Substance (g)		Physical appearances
		PEG 1000	PEG 6000	Shape	Texture	Hardness	Colour
I	1	9	0	Bullet-shaped	Very greasy and least shining	Soft	Chalky white
II	1	6	3	Bullet-shaped	Greasy and slightly shining	Slightly hard	White
III	1	3	6	Bullet-shaped	Slightly greasy and shining	Hard	Colourless white
IV	1	0	9	Bullet-shaped	Least greasy and very shining	Very Hard	Colourless 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.

Based on the observation that has been carried out, suppositories from Group 1 which contain 9g of PEG 1000 and contain no PEG 6000 has the highest intensity of white colour (chalky white) compared to the other groups. The intensity of white colour is decreasing to nearly colourless from Group 2 to Group 4 due to the presence of small amount of PEG 1000 and increasing amount of PEG 6000. Since the active ingredient that is used in the experiment is paracetamol which is white in colour, the colour of the suppositories produce will be white but differ in the transparency degree. The formulation with the lowest amount of PEG 1000 is more transparent compared to the others.

As for texture, suppositories from Group 1 are very greasy but least shining compared to the other suppositories. This is due to the presence of high amount of PEG 1000. Suppositories from our group which is Group 4 are the least greasiness due to presence of high amount of PEG 6000 and absence of PEG 1000. As for the formulation with lowest amount of PEG 1000 and highest in the amount of PEG 6000 which is suppository from Group 4, the suppository formed is the hardest of all. This is because the hardness of PEG increases with increasing molecular weight. PEG 6000 has bigger molecular weight compared to PEG 1000.  In other words, the higher the quantity of PEG 6000 in a formulation, the less greasy the suppository will be. As for hardness, we can conclude that the higher quantity of PEG 1000 (lower quantity of PEG 6000), will produce softer suppository.

1. 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.

The time needed for the suppository to melt is 74.00 minute.

Amount of PEG 6000	0		3		6		9
Groups	1	5	2	6	3	7	4	8
Time (min)	61.82	71.45	33.72	36.47	39.21	37.14	74.00	53.34

 

Amount of PEG 6000 (g)	0	3	6	9
Average of time (min) (¯x ± SD)	66.635± 4.815	35.095± 1.375	38.175± 1.035	63.67± 10.33

 

Based on the graph above, it can clearly seen that the average time needed for the suppository to completely melt decreases initially and increases with the increase of the amount of PEG 6000. The time needed for the suppository with 0g of PEG 6000 to melt is supposed to be the shortest. However, errors may have occured in the procedure of this experiment. The increase of the time needed is due to the presence of hydroxyl(OH) group in the suppository. The higher the amount of PEG 6000 used, the more the OH group that will be present in the suppository. Therefore, there will be more hydroxyl group forming hydrogen bond with paracetamol. With the increase in the formation of hydrogen bond, the suppository formed will be harder and time needed to completely melt the suppository will increase in water. This is because time needed for the dissociation of the hydrogen bond is more difficult with the increase in the formation of the hydrogen bond. From the graph, it can be seen that the average time needed for the suppository with 9g PEG 6000 increases abruptly after the time needed for suppository with 6g PEG 6000 The time taken for suppository containing 9g PEG 6000 to melt measured by both Group 4 and Group 8 has  a large difference. The time taken for suppository to melt measured by Group 8 is shorter while Group 4 is much more longer. They are not around the same range.

The inaccuracy of the result, that is the time needed for suppository with 0g PEG 6000 and the large difference of time measured for group 4 and group 8 can be due to the errors that occur in the experiment. This might due to the inappropriate temperature where higher temperature will increase the melting of the suppository, producing the shorter time needed as measured in Group 8.  Besides, the accidental addition of water from the water bath into the beaker containing suppository will also increase the dissolution of suppository as more water to dissociate the hydrogen bond. A Noyes-Whitney equation of dissolution can explain the theory behind where the additional water will reduce the value of C, concentration of solid in bulk solution. 

is the rate of dissolution.

A is the surface area of the solid.

C is the concentration of the solid in the bulk dissolution medium.

C_s is the concentration of the solid in the diffusion layer surrounding the solid.

D is the diffusion coefficient.

L is the diffusion layer thickness.

With the decrease in the value of C, the value for (C_s - C) will be larger. Hence, the rate of dissolution will be faster, time taken for the suppository to melt will be shorter. Another error that might cause the inaccuracy may be due to the stirring of water when the suppository is melting by using glass rod. Hence, these errors has to avoided in order to improve the accuracy of the experimental result.

Time (minutes)	UV Absorption
	0	5	10	15	20	25	30	35	40	45	50	55	60
UV Absorption at 520 nm	0.0	0.002	0.001	0.003	0.004	0.004	0.009	0.052	0.014	0.007	0.007	0.016	0.052

 

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

The UV spectrometer measures the release of paracetamol from the suppository in the dialysis bag to the distilled water. The release of the drugs from the suppository involved the diffusion mechanism. The water is set to 37 ⁰C to mimic the temperature of human body as suppository will be applied in the human body. Meanwhile, the dialysis bag represents the skin membrane.

The graph above shows the relationship between the UV absorption against time for paracetamol suppository. Based on the graph, it shows slowly increasing in the absorption of UV. The increasing flow continue until minutes 38 where there is a sudden decrease in the absorption. Supposingly, the UV absorption of the suppository increases when the time increases, which means that the longer the time, the higher the amount of drugs passing through the membrane or the higher the bioavailability is. Theoretically, the acceleration of UV absorption at the first 5 minutes is caused by greater hypertonicity of the content in dialysis bag compared to the surrounding distilled water.

As the experiment proceeds, the content in the dialysis bag becomes closer to isotonicity to the distilled water as some of the paracetamol has been moved to the distilled water. This will result in the reduced gradient of the graph when time passes by. If the experiment is continued beyond 60 minutes, it may result in a straight line graph as the concentration of paracetamol in the distilled water equals to the concentration of paracetamol at the dialysis bag.

Polyethylene Glycol Polymers have received much attention as suppository bases in recent years because they possess many desirable properties. They are chemically stable, nonirritating, miscible with water and mucous secretions, and can be formulated, either by molding or compression, in a wide range of hardness and melting point. Like glycerinated gelatin, they do not melt at body temperature, but dissolve to provide a more prolonged release than theobroma oil.

In this experiment, some of the precaution steps must be taken during conducting the experiment. The rope should tie both end of the dialysis bag tightly to prevent leakage of the suppository that has miscible with water. We must also stir the distilled water before sample is taken out for measurements to ensure uniform distribution of the released active ingredient. Besides, the smooth surface of the cuvette should not face the source of UV light and the smooth surface should be cleaned before it is placed into the device.

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

Time (min)		Average of the UV absorption at 520nm (x  ± SD)
		0	5	10	15	20	25
Suppository	I	0.0040 ± 0.0014	0.0155± 0.0106	0.0265± 0.0134	0.0325± 0.0092	0.0410± 0.0127	0.0460± 0.0127
	II	0.0120± 0.0113	0.0310± 0.0127	0.0345± 0.0035	0.0390± 0.0226	0.0475± 0.0106	0.0455± 0.0247
	III	0.0230± 0.0084	0.0395± 0.0212	0.0530± 0.0396	0.0645± 0.0502	0.0705± 0.0530	0.0755± 0.0559
	IV	0.0035± 0.0050	0.0220± 0.0283	0.0080± 0.0099	0.0110± 0.0113	0.0110± 0.0099	0.0115± 0.0106

Time (min)		Average of the UV absorption at 520nm (x  ± SD)
		30	35	40	45	50	55	60
Suppository	I	0.0555± 0.0205	0.0555± 0.0106	0.0605± 0.0162	0.0720± 0.0311	0.0880± 0.0467	0.1005± 0.0431	0.1925± 0.0516
	II	0.0595± 0.0205	0.0750± 0.0141	0.0655± 0.0191	0.1135± 0.0473	0.0850± 0.0156	0.0925± 0.0233	0.0900± 0.0297
	III	0.0845± 0.0693	0.0940± 0.0693	0.1115± 0.0742	0.1290± 0.0707	0.1335± 0.0742	0.1305± 0.0629	0.1915± 0.1435
	IV	0.0175± 0.0120	0.0405± 0.0162	0.0325± 0.0261	0.0275± 0.0290	0.0385± 0.0445	0.0475± 0.0445	0.0660± 0.0198

 

Based on the graph plotted, it can be seen that suppository I has the highest UV absorption. This means that the amount of paracetamol present in the solution is the highest. This may be caused by the presence amount of hydroxyl group is higher in PEG 1000 compared to PEG 6000. Higher number of hydroxyl group in PEG result in more availability of it to react with water and thus make it more miscible with water and higher percentage content of paracetamol to diffuse out of the dialysis bag. Amount of PEG 1000 used in suppository will affect the distribution of hydrophilic and hydrophobic phase. Paracetamol is a hydrophilic drug depend on the amount of PEG 1000 been used in this experiment. So, when the dialysis bag is immersed in the water, water diffuses into the dialysis bag via osmosis. This causes the paracetamol to dissolve in the presence of water. Due to the miscibility of water and PEG base, the dissolved paracetamol will diffuse out of the dialysis bag into the water medium. This causes the UV absorption measured to be the greatest.

On the other hand, suppository IV has the slowest rate of drug released which accounts for its lowest UV absorption in this experiment. This is because of the high amount of PEG 6000 which contain less amount of hydroxyl group in its structure make it immiscible with water. Therefore the amount of paracetamol to diffuse out of the dialysis bag is smaller and resulted in the less present of paracetamol in the water bath when reading is taken. Besides, PEG 6000 has the characteristic of higher viscosity make it less available to miscible with water. This causes the drug to be difficult to diffuse out into the water. As increased of PEG molecular weight resulted in decreased solubility in water and solvent. From the graph, we can see that there is repeated in decrease of the UV absorption reading when at a certain time the reading is increased.  This resulted in undesired reading of UV absorption. This may be due to errors while conducting the experiment. Some of it might be uneven stirring of the solution in the beaker before the solution is taken to be filled in the cuvette. Thus amount of paracetamol that has diffuse out into the water medium is uneven distributed.

Suppository III is the second lowest UV absorption value while suppository II has the second highest UV absorption value. This result can be said accurate as the PEG 1000 used for suppository II and III are 16g and 3g respectively. The UV absorption value of suppository II is higher than suppository III. Therefore, the UV absorption value of suppository II is definitely higher than suppository III, which is shown in the graph. Proper ratio of the two bases will enable optimum and constant release of drug into the environment. When water diffused in, PEG 1000 will miscible with water evenly where the drug can dissolves in water. Therefore, constant rate of release of drug can be achieved. 

There are several precaution steps that must be taken when using the UV spectrophotometer. Firstly, don't touch the optical surface of cuvettes with fingers to avoid erratic reading. Then, do not overfill or under fill the cuvette, the cuvette should be three-fourth full. Besides, preserve the instrument from dust particles. Moreover, never wash the cuvettes with chromic acid. Wash the cuvette with the distilled water and then with methanol before storage.