Experiment 4: Evaluation of The Effect of Different Formulation on Suppository Characteristics

TITLE:

Evaluation of The Effect of Different Formulation on Suppository Characteristics

DATE OF EXPERIMENT:

20th MAY 2015

OBJECTIVES:

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

INTRODUCTION:

Suppository is a solid formulation of different sizes and shapes suitable for rectal drug administration. Good suppository will melt after the rectal administration and release the drug either topically or systematically.

The drug needs to be dispersed in suitable suppository bases. Good bases are not toxic, no irritation, will not interact with other drugs and also easy to be mould into a suppository. Different composition on base will affect the rate and limit of release of the drug 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 beaker

Hotplate

5ml measuring cylinder

Suppository mould set

Water bath 37^oC

Dialysis bag

Glass rod

5ml pipette

Kuvets plastics

Spectrophotometer UV/Vis

REAGENTS:

Polyethylene glycol (PEG) 1000

Polyethylene glycol (PEG) 6000

Paracetamol

Distilled water

EXPERIMENTAL PROCEDURE:

1. Paracetamol saturated stock solution is prepared by adding 10g of Paracetamol in 5ml distilled water.

1. 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	0	1	10
II	2,6	6	3	1	10
III	3,7	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.

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

3. 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:

Time (min)		UV absorption at 520nm
		0	5	10	15	20	25	30
Suppository	I	0.013	0.197	0.287	0.208	0.211	0.226	0.297
	II	0.020	0.025	0.031	0.034	0.034	0.036	0.036
	III	0.002	0.003	0.004	0.007	0.021	0.013	0.019
	IV	0.000	0.002	0.003	0.003	0.004	0.004	0.005
	V	0.0013	0.0045	0.0074	0.0068	0.0082	0.011	0.011
	VI	0.000	0.0012	0.014	0.011	0.012	0.011	0.016
	VII	0.020	0.033	0.030	0.010	0.023	0.013	0.013
	VIII	0.010	0.018	0.078	0.033	0.046	0.044	0.046

Time (min)		Average UV absorption at 520nm (  x ± SD)
		0	5	10	15	20	25	30
Suppository	I	0.007±0.008	0.100±0.136	0.147±0.183	0.107±0.142	0.110±0.143	0.119±0.152	0.154±0.202
	II	0.010±0.010	0.013±0.017	0.023±0.012	0.023±0.016	0.023±0.016	0.024±0.018	0.026±0.014
	III	0.011±0.013	0.018±0.021	0.004±0.027	0.009±0.002	0.022±0.001	0.013±0.000	0.016±0.000
	IV	0.005±0.007	0.010±0.011	0.041±0.053	0.018±0.021	0.025±0.030	0.024±0.028	0.026±0.029

Discussion:

1. Compare and discuss the physical appearance of the suppository formed.

Physical characteristic	Suppositories
	I 1, 5,	II 2, 6	III 3, 7	IV 4, 8
Shape	Bullet shaped, solid	Bullet shaped, solid	Bullet shaped, solid	Bullet shaped, solid
Hardness	+	++	+++	++++
Greasiness	++++	+++	++	+
Colour	White	White	White	White

Different composition of the PEG 1000 and PEG 6000 in the formulation of the suppository will affect the physical characteristic of suppository. PEG is a suppository base that soluble in water but is rarely use now due to its hydrophilic effect. It can retain drug and affect  the rate of release of drug. PEG 1000 is less hydrophilic compare to PEG 6000 because PEG 6000 contain of more hydroxyl group (-OH).

Hardness is increasing with the increasing of composition of PEG 6000 from the Suppository I to IV. This shows that Suppository IV is the hardest one. Because there is more hydrogen bonding formed in this suppository. PEG 6000 also increasing the clarity of the suppository, all the suppositories are in white color

Besides that, Suppository I to IV have decreasing waxy properties due to the decreasing of the composition of PEG 1000. PEG 1000 is less hydrophilic and has more lipophilic property. Therefore, suppository with the high content of PEG 1000 composition will make the suppository more waxy as like the Suppository I. While for the Suppository IV, it is less waxy and looks very dry due to the absent of the PEG 1000. Moreover, PEG 6000 also increasing the clarity of the suppository. All the suppositories show white in colour.

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

Suppository	Group	Time needed to melt the suppository
I	1	65 minutes
II	2	10 minutes
III	3	60 minutes
IV	4	74 minutes
I	5	58 minutes
II	6	65 minutes
III	7	43 minutes
IV	8	61 minutes

Amount of PEG 6000	0	3	6	9
Time average (min) (x ± SD)	61.5 ± 4.95	37.5 ± 38.89	51.5 ±12.02	67.5 ±9.19

Generally, we know that the time required to melt a suppository is increased with the increased amount of PEG 6000 added. The time needed to melt the suppository is increasing with amount of PEG 6000 added because a high composition of PEG 6000 contribute to more of hydroxyl groups (-OH) that are capable to form strong hydrogen bonds between molecules of PEG 6000 and paracetamol. Therefore, longer time is needed to break the bond in order for the suppository to melt and release the drug.

But, there is a result deviate from theory which occurred durring the IV suppository. This may mainly due to the  experimental errors. The errors might be our failure to control the temperature of water bath, weighing error or time measured error.

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

                                    Suppository with the formula IV

Time (min)	0	5	10	15	20	25	30
UV absorption at 520nm	0.010	0.018	0.078	0.033	0.046	0.044	0.046

Y-axis=UV absorption value

X-axis=time (min)

The graph shows the UV absorption of suppository IV against time. According to the theory, the UV absorption of suppository generally shall increase as time passes, and the data obtained shall lead to the plot of a sigmoid-shaped graph. However in our group doing suppository with formulation IV, the UV reading of the drug is increasing slowly with a small amount then increase drastically at 5^th minutes and followed by decrease as well as increase after 15^th minutes.

             Errors may be occur during the preparing the suppository procedures. Paracetamol molecules may be not disturbed evenly in the suppository formed. This can lead to the uneven releasing of paracetamol from the formulation to occur. Besides that, water from the water bath may be mixed into the mixture in the beaker and thus decrease the UV absorption. Other than that, it may be our fault when we are taking the sample without mixing the water surrounding the suppository. This causes the amount of paracetamol amount in each time sample taken is a large difference and thus affect the UV absorption.

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

Time (min)		Average UV absorption at 520nm (  x ± SD)
		0	5	10	15	20	25	30
Suppository	I	0.007±0.008	0.100±0.136	0.147±0.183	0.107±0.142	0.110±0.143	0.119±0.152	0.154±0.202
	II	0.010±0.010	0.013±0.017	0.023±0.012	0.023±0.016	0.023±0.016	0.024±0.018	0.026±0.014
	III	0.011±0.013	0.018±0.021	0.004±0.027	0.009±0.002	0.022±0.001	0.013±0.000	0.016±0.000
	IV	0.005±0.007	0.010±0.011	0.041±0.053	0.018±0.021	0.025±0.030	0.024±0.028	0.026±0.029

The graph obtained shows that suppository with formulation I and IV obey the sigmoid curve except the suppository with the formulation II and III. This is because there is a high value of UV absorption at the beginning and then decrease drastically and increase again. This shows the unusual sigmoid curve.

            Formulation I suppository has the highest peak since it contains the least amount of PEG 6000  means that it has the highest rate of drug release compared to others formulation type.

            Formulation II and III has 3 and 6 g PEG 6000, thus suppose suppository with formulation II has higher rate of drug release compared to III which has higher amount of PEG 6000 when time increase. And the graph obtained was actually go according to the theory.       

Formulation IV contains the highest amount of PEG 6000 among others, it should have slowest releasing degree of the drug, but in the experiment, it has the second highest drug release after formulation I (given as the UV absorption), suppose the curve obtained is flat at the beginning then increase very slowly, it should require the longest time to reach the highest value of drug release, as the suppository is the hardest.

            These can only be explained by taking into account the errors that might occur in the experiment. Uneven stirring of the solution, unstable temperature, mistake in the suppository formation, impurities can all lead to the experimental errors.

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:

The different amount of combination of PEG 1000 and PEG 6000 in the suppository preparation affects the physical characteristics e.g. greasiness texture, and shape of the suppository as well as the rate of release of the active ingredient.

 REFERENCES:

1.      Pharmaceutical Practice.(1996). Diana M.Collett Micheal E.Aulton.Pulished by Churchill Livingstone.

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

3.   http://www.pharmaceutics.comoj.com/PDF/Suppositories_PHR308.pdf