Date : 6 MAY 2014
Title of experiment:
The effects of differences characteristic of active ingredient in formulation of suppository.
Objectives:
1) To study the effects of difference amount of polyethylene glycol used in the formulation of suppository.
2) To describe and elaborate the texture, clarity and colour of suppository formed.
Introduction
Suppositories are solid, bullet-shaped preparations designed for easy insertion into the anus (back passage). The suppository dissolves at body temperature and gradually spreads over the lining of the lower bowel (rectum), where it is absorbed into the bloodstream.
Suppositories are used either to provide a local action in the rectum, or as an alternative to oral forms of medicine (example when someone is continuously feeling sick or is unable to take anything by mouth). The medicine is easily absorbed from the rectum as there is a rich supply of blood vessels in this area.
In this experiment we want to know how the difference of base composition used will influence the suppository’s action on releasing its active ingredient/s.
Procedure
1. Saturated stock solution of paracetamol was prepared( 10 g in 5 ml of distilled water).
2. 10 g Paracetamol suppository was prepared using following formula:
3. Suppository was formed by using suppository-mould to get its shape. The shape, texture and colour of suppository that are formed was observed and described.
4. One suppository was incorporated into the beaker that containing 10 ml of distilled water (37 degree Celsius) and the time taken for it to melt was recorded.
5. One suppository was incorporated into the dialysis bag. After that, the bag was incorporated into the beaker that containing 50 ml of distilled water that already heated into 37 degree Celsius.
6. 3-4 ml of sample was pipette at every 5 minutes and the liberation of paracetamol from suppository was determined by using uv-visible spectrometer. Make sure distilled water is stirred using glass rod before taking the sample.
Result
result procedure no 3
result for procedure no 6
Discussion
1. compare the physical shape of suppositories that are formed in this experiment and give the comment.
In this experiment, all the suppositories formulated have the shape of a torpedo or torpedo-shaped due to all suppositories was made using moulds of similar torpedo shape. The quantities of PEG 1000 and PEG 6000 are different for each group. This leads to formation of suppositories with different physical characteristics.
In terms of texture, greasiness of the suppositories increases with increasing of amount of PEG 1000. This explains the decrease of degree of greasiness from suppository I to IV, as amount of PEG 1000 decreases from suppository I to IV. On the other hand hardness can be associated with amount of PEG 6000 in the suppositories. Note that increasing amount of PEG 6000 and decreasing amount of PEG 1000 in the suppositories in turn increases the hardness of the suppositories. This is due to hardness of PEGs increases with its molecular weight. It can be simply said that increasing the quantity of PEG 6000 in the formulation will yield suppositories with less greasiness and more hardness. However a suppository which is too hard and not greasy may cause pain during administration, thus this issue should be taken into consideration when formulating suppositories.
About the color of the suppositories, all of them are generally white. This is due to paracetamol used as the ingredient in the suppositories is white in color. However, the degree of transparency of the color in question differs between the suppositories. From suppositories I to IV transparency of the white color increase due to decreasing amount of PEG 1000 available. Note that amount of paracetamol in all suppositories are the same which is 1 mL.
2. plot a graph of time taken for suppository to melt against amount of PEG 6000 in a formulation.
Two types of PEG has been used in this experiment which are PEG 1000 and PEG 6000. A graph of mean time versus amount of PEG 6000 has been plotted. Initially, the graph increasing gradually and then it were decreased. Polyethylene glycol (PEG) which having average molecular weight of greater than 1000 are wax-like, white solids with the hardness increasing with an increase in the molecular weight. Combination between PEG 1000 and PEG 6000 in this experiment is to achieve a suppository base of the desired consistency and characteristics.
When the PEG 6000 is absence, the mean time is 36.49 minutes, while the mean time amount of PEG 6000 3g is 42.78 minutes. When the amount of PEG 6000 is 6g, the mean time is 39.68 minutes and when amount of PEG 6000 is 9g, the mean time is 37.16 minutes. The mean time for suppository to melt is decreasing when the amount of PEG 6000 is increasing. However, there is an inaccuracy of result. 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. Plot the graph of UV absorption versus time. Give explanation.
Graph of UV absorption at 520nm versus Time ( group 8)
In this experiment, the suppository is put into a dialysis bag and immersed in a 37oC water bath. The release of paracetamol from the suppository into the water is determined by the UV absorption. The paracetamol in the water sample that released from the dialysis bag will absorb ultraviolet radiation of 520nm. Thus, the intensity of UV absorption is directly proportional to the concentration of paracetamol present in the water sample. This meant that the UV absorption reading should be increased when the time is increased as the more paracetamol is released from the dialysis bag.
The graph above shows the UV absorption at 520nm for suppository 3 which contain 0g of PEG 1000 and 9g of Peg 6000. We can observe that the graph is up and down as time is increase. Theoretically, the graph should show a sigmoidal shape. This is due to the suppository will dissolve slowly and the drugs are released from the dialysis bag. So that, the concentration of drugs in the water is increases as the time increased until all the drugs are released and the concentration of drug inside the dialysis bag is equal to the concentration of drug in the distilled water (isotonic). Once the equilibrium is reached, there is no movement of drug and the graph will become constant.
At time 0, the solution surrounding the dialysis bag is tested for the UV absorption. Theoretically, there should be no value for UV absorption as the diffusion has not occurred yet as there is no paracetamol in the solution. This error mybe due to delayed taking the sample which little bit paracetamol has been released from dialysis bag.
From the graph obtained, the graph are keep on increasing of UV absorption with time except at the time of 10 minutes and 35 minutes there shows a drop of the value and cause different from the theoretical. This is due to error while hamdling the experiment.For example, the solution is not stirred well before taking solution to investigate and this will affect the result obtained. This may also due to the accidentally pouring of the distilled water in the beaker and this can cause the changed in the concentration of the drug. Other than that is, due to bubble present. This will affect the UV absorption.
4. plot a graph of UV absorption against time for formulation suppository that have different composition. give comment.
The higher the absorption of UV, the higher the amount of drug in the solution based on the equation where based on the Beer-Lambert law
A = εbc
ε=molar absorptivity of the compound or molecule in solution (M-1cm-1)
b= path length of the cuvette or sample holder (usually 1 cm)
c = concentration of the solution (M)
As the suppository dissolve in the dialysis bag over time, the drug is released from the suppository and the concentration of the drug in the solution increases, leading to the increase of absorption of UV over time as stated in the Beer-Lambert law at the graph. However again due to errors in conducting the experiment, there is significant fluctuation observed on suppository I and II.
Theoretically, the highest absorption UV should be suppository I, followed by II, III and IV. However, due to error in experiment techniques such as parallax error, handling the equipments such as cuvette, pipette, the UV spectrometer etc, the result is different from the theory, where Suppository I has the highest absorption of UV at 520nm, followed by IV, III and II.
Suppository IV has the highest amount of PEG 6000, followed by III, II and I. PEG 6000 is a high molecular weight with long chain length. The higher the amount of high molecular weight PEG, the higher the melting point and the firmer the suppository would be. High concentration of high molecular weight PEG will also lengthen the dissolution time of the suppository, which reduces the drug release. This will lower the concentration of drug in the solution and causes lower absorbance of UV.
5. What are the functions of each of the ingredient used in the suppository formulation? How the different amount of PEG1000 and PEG6000 used can interfere with the physical characteristic and the rate release of the suppository preparation.
Paracetamol is a NSAID, having only anti-pyretic activity and analgesic effect, but no anti-inflammatory activity like other NSAIDs. Paracetamol has very low water-solubility. Thus, it should be homogenously dispersed in a water-soluble suppository base. It should not be dissolved in the base because this can reduce the release rate of Paracetamol.
PEG 1000 and PEG 6000 are the examples of water-soluble suppository base used. The base acts as a carrier for the drug. It is designed to dissolve or disperse within the rectal mucosa, so that the drug homogenously dispersed within can be delivered into the plasma via diffusion through the plasma membrane. Then, the drug will exert its effect either locally or systemically.
In the perspective of physical characteristics, a high molecular weight PEG can increase hardness, but decrease the stickiness and the hygroscopicity of the suppositories in the order from I to IV. This is because there is more abundant hydrogen bondings in the PEG used.
The higher the amount of the high molecular weight PEG (eg PEG 6000), the slower will be the drug release rate from the suppository. Similarly, PEG 1000 can cause drug release rate to be faster. This can be proven by the decrease in the average UV absorbance from suppository I to suppository IV, when the amount of PEG 6000 increases. This is because suppository IV which consist of polyethylene glycol 6000 only form more hydrogen bonds within itself thus release the drug at the slowest rate.
A combination of both PEG 1000 and PEG 6000 is beneficial, both to the physical characteristics and the drug release rate. A softer, less brittle preparation can be produced, where the drug is dispersed and liberated at a moderate rate. This is very important in ensuring that a certain amount of drug is constantly absorbed, and avoiding leakage of drug from the rectum which can be a waste.
Conclusion
As a conclusion, all the suppositories formulated have the torpedo-shaped.In terms of texture, greasiness of the suppositories increases with increasing of amount of PEG 1000. Increasing amount of PEG 6000 and decreasing amount of PEG 1000 in the suppositories in turn increases the hardness of the suppositories. About the color of the suppositories, all of them are generally white.
The release of paracetamol from the suppository into the water is determined by the UV absorption. Thus, the intensity of UV absorption is directly proportional to the concentration of paracetamol present in the water sample means that the UV absorption reading should be increased when the time is increased as the more paracetamol is released from the dialysis bag.
Theoretically, the highest absorption UV should be suppository I, followed by II, III and IV.However in this experiment, the result that we get is Suppository I has the highest absorption of UV at 520nm, followed by IV, III and II.
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