Lab Report : Suppository
EFFECTS OF DIFFERENT COMPOSITIONS OF MATERIALS ON THE CHARACTERISTICS OF SUPPOSITORY FORMULATION.
Date of Experiment: 6th May 2013
Lecturer’s Name: Dr. Ng Shiow Fern
Aims:
1. To determine the effects of different composition of base on the physical characteristics of suppositories.
2. To determine the effects of different composition of base on the rate of drug release.
Introduction:
Suppository is a medicated formulation which consists of different sizes and shapes. Making the drug more suitable to be administered to patient through rectum, vagina or urethra. It is generally conical or bullet shape. The ideal suppository bases must be able to melt at body temperature, 370C, non irritating, physically and chemically stable, inert, high viscosity when melted and then to release the drug locally or systemically. Bases that is more widely used in a formulation is cocoa butter which are innocuous, bland , non reactive and melts at body temperature. The amount of dose of drug incorporated into a suppository depends on the release properties of the base.
Suppository is taken when a person unable to take medicine orally and is mainly used to treat constipation. The advantage of suppository is that it can prevent first pass effect ,and to avoid the digestive enzyme and thus increase bioavailability. The suppository can be targeted delivery system and get to site of action with lower dose. This will reducing systemic toxicity. If there is severe nausea or vomiting it is advisable to use suppository as well. But, suppository have some disadvantages. It can cause mucosal irritation, patience compliance, erratic and undesired absorption. If patient with diarrhea and disease state will affect absorption.
The action level of suppository depends on the nature of drug, types of bases, concentration of drugs and absorption rate of targeted site. The pH of the mucosal is important for drug absorption. Weak acids and bases can be absorbed more effective than strong acids and bases. This is due to highly ionized drugs are poorly absorbed. Drug has to be incorporated into a suitable suppository base in order to deliver the drug efficiently to the targeted site. A different composition of suppository base will influence the drug release rate. If a drug is more soluble in base, this will slow down the release rate of drug from suppository. On the contrary, a drug which is less soluble in base will be more readily released. A good base must not cause toxicity, does not cause irritation, does not react with the drug and easy to form suppositories. In this experiment, water-soluble base, polyethylene glycol is used.
Apparatus:
Weighing balance Water-bath(370C)
Weighing boat Dialysis bag (10cm)
Spatula 2 strands of thread
50ml beaker Glass rod
100ml beaker 5ml pipette set and pipette bulb
Hotplate 1 plastic cuvette
5ml measuring cylinder UV spectrophotometer
1 set of suppository mould
Materials:
Polyethylene glycol (PEG) 1000
Polyethylene glycol (PEG) 6000
Paracetamol
Procedure:
1. Saturated stock solution of paracetamol is prepared. (1g of paracetamol is added to mixture of PEG 1000 and PEG 6000).
2. 10g of paracetamol suppository is prepared using the following formula:
|
Suppository |
Group |
Ingredient (g) |
Total (g) |
||
|
PEG 1000 |
PEG 6000 |
Paracetamol stock solution |
|||
|
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. Suppositories are shaped by using suppository-mould. The shape, texture, and colour of the suppositories are being examined.
4. 1 suppository is placed into the beaker containing 10ml of saline water at 370C and time required to melt the suppository is recorded.
5.1 suppository is filled into dialysis bag. Two terminal end of the bag is assured to be tied up neatly. The dialysis bag is placed into the 100ml beaker which containing 50ml saline water being heated up to 370C.
6. An aliquot sample with 3-4ml is pipette at 5 minutes interval. The rate of release of paracetamol from the suppository is determined using UV-visible spectrometer. Make sure saline water is stirred by glass rod before sample is taken out.
Results:
1. Compare the physical appearance of the suppository formed.
|
Characteristics |
I |
II |
III |
IV |
|
Shape/Appearance |
Bullet-shape, Half transparent solids |
|||
|
Colour |
White |
|||
|
Texture |
White Paracetamol drug is seen dispersed in the half transparent PEG suppository base |
|||
|
Hardness |
+ |
++ |
+++ |
++++ |
|
Greasiness |
++++ |
+++ |
++ |
+ |
|
Stickiness |
++++ |
+++ |
++ |
+ |
|
Hygroscopicity |
++++ |
+++ |
++ |
+ |
Besides that, the colures of all suppositories is white. The intensity of this suppositories with different contents of PEG 6000 is undistinguishable. We can say that the differences in formulation have no effect on the colour intensity of the suppository as there is no difference in the colour of the raw PEG 1000 and PEG 6000.
The hardness of the suppositories increases when the amount of PEG 6000 increases but the stickiness decreases. This is because PEG 6000 contains higher content of hydroxyl groups within the structure. More of intra-molecular and intermolecular hydrogen bonds are formed between PEG molecules, thus rendering the overall structure strength, and the suppositories formed are less sticky in nature. Higher energy or forces is needed to break up these interactions, so the suppositories are harder and harder.
Moreover, the greasiness of the suppositories decreases from suppository I to suppository IV. However, PEG is a water-soluble suppository base. Thus, there will not be any feeling of greasiness on the suppositories produced.
Hygroscopicity means the ability of absorbing moisture. The hygroscopicity of the suppositories decreases when the amount of PEG 6000 increases. This may be due to the increasing percentage of hydrogen bonding within structures. The abundant hydrogen bonds between PEG are stronger than the bonding between the PEG and water molecules in the air. As a result, it is becoming more and more difficult for the suppositories to absorb water readily, with increase the amount of PEG 6000. The higher amount of PEG 1000 will absorbed more of water from air.
2. Plot a graph of time needed to melt suppository versus amount of PEG 6000 in the formulation. Compare and discuss the result.
|
Suppository |
Group |
Time needed to melt the suppository |
|
I |
1 |
55 minutes 14 seconds |
|
II |
2 |
30 minutes |
|
III |
3 |
36 minutes 46 seconds |
|
IV |
4 |
55 minutes 47 seconds |
|
I |
5 |
37 minutes 37 seconds |
|
II |
6 |
56 minutes 18 seconds |
|
III |
7 |
30 minutes 14 second |
|
IV |
8 |
55 minutes 52 seconds |
| Amount of PEG 6000 (g) | 0 | 3 | 6 | 9 |
| Mean time (min) (x ± SD) | 46.425 ± 8.805 | 43.15 ± 13.15 | 33.5 ± 3.27 | 55.825 ± 0.045 |
Graph 1
Polyethylene glycol (PEG) is a polyether compound which being applied in many application from industrial manufacturing to medicine. In this experiment, PEG is used as the suppository base. Two types of PEG which are PEG 1000 and PEG 6000 are being used in this experiment.
A graph of mean time versus amount of PEG 6000 has been plotted. The suppository is placed in a beaker containing 10mL distilled water with temperature of 370C and the time needed to melt the whole suppository is recorded.
There are comparisons of mean time needed to melt the suppository with a different amount of PEG 6000. When the amount of PEG 6000 is none, the mean time needed is 46.425 minutes, while the mean time needed shows 43.15 minutes when amount of PEG 6000 is 3g. The mean time needed is 33.5 minutes when the amount of PEG 6000 is 6g and when amount of PEG 6000 is 9g, the mean time is 55.825 minutes. The mean time needed is decreasing when the amount of PEG 6000 is increasing. However, there is an inaccuracy of result occur when the mean time increase when using 9g of PEG 6000 compare to 6g of PEG 6000. This may be due to some errors when experiment is carried out. For example, the water temperature has not reach 37ᴼC when the suppository is put in the water bath.
Melting point of PEG is generally above body temperature. The high melting point also means that the bases do not melt in the body but dissolve and disperse the medication slowly, providing a sustained effect.
3. For each 5 minutes, an aliquot sample (3-4mL) is pipette and determines the release of Paracetamol from the suppository by the spectrometer UV-visible. Make sure the distilled water is stir with the glass rod before the sample is taken.
| Time (min) |
UV-visible absorption |
||||||||||||
|
0 |
5 |
10 |
15 |
20 |
25 |
30 |
35 |
40 |
45 |
50 |
55 |
60 |
|
| UV absorption at 520nm |
0.0 |
0.083 |
0.023 |
0.032 |
0.023 |
0.060 |
0.058 |
0.073 |
0.091 |
0.083 |
0.102 |
0.089 |
0.118 |
Graph 2
Based on the graph plotted, at the first 5 minutes, the UV absorption was very high, decreasing after 5 minutes and generally, as the time increases, the UV absorption also increases. Unfortunately, looking closer into it, there’s slightly decrease after each elevated UV absorption. This may be due to instrumental or operational error during the experiment as the ideal UV-visible absorption should increase gradually over time.
Our group had prepared suppository II which contain 6g of PEG 1000, 3g of PEG 6000 and 1g of Paracetamol. Polyethylene glycols are polymers of ethylene oxide and water, prepared to various chain lengths, molecular weights, and physical states. Polyethylene glycols (PEGs) having average molecular weights of 300, 400, and 600 are clear, colorless liquids, while those with molecular weights of 600-1000 are semisolids. Those having average molecular weights of greater than 1000 are wax-like, white solids with the hardness increasing with an increase in the molecular weight. These polyethylene glycols can be blended together to produce suppository bases with varying: melting points, dissolution rates and physical characteristics. Drug release depends on the base dissolving rather than melting.
Polyethylene glycols are water soluble polymers that often melt at temperatures higher than the rectal or physiological temperature of 37°C. Consequently, when used in rectal formulations, the drug is released gradually, as a result of the progressive dissolution of the PEG excipients in an aqueous dissolution medium. High molecular weight PEGs have high melting points, and consequently have slower dissolution rates, compared to PEGs of intermediate molecular weight and this was the basis of formulating the PEG 1000/6000 blend. PEG 6000 released paracetamol at a slower rate than PEG 1000.
Therefore, a few steps of precaution need to be taken in order to achieve a better and accurate result. Before the sample is taken to the UV spectrometer, the distilled water inside the beaker must be stirred first. Besides, the cuvette must be wiped before place it inside the spectrometer. Other than that, the UV spectrometer must be under a good condition in order to have a good result.
4. Plot graph of UV absorption against time for the suppository formulation with different compositions. Discuss and compare the results.
|
Time |
UV absorption average at 520nm (x ± SD) |
|||||||||||||
|
0 |
5 |
10 |
15 |
20 |
25 |
30 |
35 |
40 |
45 |
50 |
55 |
60 |
||
|
suppository |
I |
0 |
0.022 |
0.023 |
0.024 |
0.0255 |
0.0265 |
0.0295 |
0.0385 |
0.040 |
0.0435 |
0.0465 |
0.056 |
0.06 |
|
|
± |
± |
± |
± |
± |
± |
± |
± |
± |
± |
± |
± |
± |
|
|
|
0 |
0.0127 |
0.0141 |
0.0156 |
0.0148 |
0.0148 |
0.0177 |
0.0219 |
0.0212 |
0.0205 |
0.0233 |
0.0226 |
0.0184 |
|
|
II |
0 |
0.0575 |
0.0295 |
0.0365 |
0.0350 |
0.0535 |
0.0530 |
0.0625 |
0.072 |
0.07 |
0.0815 |
0.079 |
0.107 |
|
|
|
± |
± |
± |
± |
± |
± |
± |
± |
± |
± |
± |
± |
± |
|
|
|
0 |
0.03606 |
0.00919 |
0.00636 |
0.01697 |
0.00919 |
0.00707 |
0.01485 |
0.02687 |
0.01838 |
0.02899 |
0.01414 |
0.01556 |
|
|
III |
0 |
0.0305 |
0.034 |
0.036 |
0.038 |
0.0445 |
0.0525 |
0.06 |
0.066 |
0.067 |
0.0745 |
0.0815 |
0.0935 |
|
|
|
± |
± |
± |
± |
± |
± |
± |
± |
± |
± |
± |
± |
± |
|
|
|
0 |
0.01202 |
0.01273 |
0.01414 |
0.01556 |
0.01485 |
0.01202 |
0.024 |
0.0269 |
0.024 |
0.0332 |
0.0361 |
0.0431 |
|
|
IV |
0 |
0.0175 |
0.0205 |
0.0255 |
0.03 |
0.034 |
0.0365 |
0.0375 |
0.044 |
0.051 |
0.059 |
0.0625 |
0.0655 |
|
|
|
± |
± |
± |
± |
± |
± |
± |
± |
± |
± |
± |
± |
± |
|
|
|
0 |
0.00636 |
0.00778 |
0.00212 |
0.00141 |
0.00424 |
0.00778 |
0.0064 |
0.0085 |
0.0085 |
0.0099 |
0.0092 |
0.0050 |
|
Graph 3
Graph 4
Ultraviolet spectrometer or ultraviolet-visible spectrophotometry refers 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. By using this technique, a light is passed through the sample that we are going to measure. When light travels through the sample, it loses energy, also known as attenuated. Therefore, if the sample contains the suspended particles, the attenuation of light will change due to a variety of scattering and absorption patterns. The changes of energy of the light are then be measured to indicate the size distributions of the particles in the sample.
Dialysis tubing is actually a semi-permeable membrane when it is used in water. It is made up from regenerated cellulose. Dialysis tube has been used in the experiment for illustrating osmosis and pressure gradients across a membrane. As it is semi-permeable, therefore it only allows certain molecules to pass through by diffusion and it will block some molecules such as polar compound to pass through the membrane. Diffusion is the movement of particle from the region of high concentration to the region of low concentration until equilibrium is reached.
In the experiment, dialysis tube had been use to determine the ability of the paracetamol of suppository to pass through the membrane and enter into the water. The amount of the sample that passed through the dialysis tube is measured by using the ultraviolet spectrophotometry. Dialysis tube indicates the human’s biological barrier. Based on the results, we can see that UV absorption at 524 nm is increasing with time for each of the suppositories. Increasing in UV absorption indicates that there is increasing in the numbers of particle of the suppositories diffuse through the dialysis tube membrane.
From the graph above, the value that has been obtained is not accurate because in this experiment, the suppository I has lowest drug release (given as the UV absorption). However, it should be the highest among the four suppositories since it has the highest amount of the PEG 1000. In theory, the hardness of the polyethylene glycol will increase with increasing molecular weight. So, as the suppository becomes harder, it should required longer time to dissolve the drug and passing through the dialysis tube membrane. Polyethylene glycol with molecular weight from 600 to 1000 is presence in the semisolid form and molecular weight higher than 1000 is wax-like form. Therefore, suppository I should has the highest UV absorption.
High proportion of high polyethylene glycol produce suppository which release drug slowly and also brittle. Suppository IV has the highest proportion of PEG 6000 which will produce the hard suppository that difficult to dissolve. The result of the experiment can be considered same as the theory. In order to prepare less brittle suppository with release drug more readily, high molecular weight should be mixing with medium or low molecular weight of polyethylene glycol.
Since PEG is nonionic substances, they are quite soluble in hard water or in other aqueous solution of various salts. Suppositories can be formulated with much higher melting point to be melting at body temperature and dissolve in body fluids. Graph become not accurate may be because of the error that has been done during the experiment. May be error occur in taking sample by pipette to measure dispersion of paracetamol using spectrometer UV-visible.
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:
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. Rita Bhatta and Mohammad Salim Hossain, 2011. Evaluation of Kollidon SR based Ketorolac Tromethamine Loaded Transdermal Film. Journal of Applied Pharmaceutical Science 01 (08); 2011: 123-127. http://japsonline.com/vol-1_issue-8/23.pdf
2. onlinelibrary.wiley.com/doi/10.1002/jps.2600640706/pdf
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