SUPPOSITORY

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

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, water bath 37^oC, dialysis bag, glass rod, 5ml pipette,  plastic cuvette, spectrophotometer UV/Vis

Materials:

Polyethylene glycol (PEG) 1000, Polyethylene glycol (PEG) 6000, paracetamol, distilled water

Methods:

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:

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

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

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

Dialysis bag

    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:

Figure 1: Physical appearance of suppositories 

Discussion:

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

Basically the shapes of all suppositories are torpedo because we used similar type of mould. Based on smoothness and hardness of the suppositories comply with the standard suppository which has smooth surface and perfect hardness. The suppositories are not too hard which may cause bad disintegration process and not too soft which may cause problem when insert the drug into the rectum area. The different in oily surface of suppository of each group may due to the amount of liquid paraffin used during lubricating the mould. The colour of the suppository that used high amount of PEG 1000 is more even white compare to suppository that used high a amount of PEG 6000. This is due to the characteristics of the PEG itself, PEG 1000 is more whitish and smooth compare to PEG 6000. In conclusion, to the ingredient used is the main cause that contribute to the physical characteristics and the rate of the drug release via rectal route.

    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.

PEG 6000 is a suppository base and theoretically, increasing the mass of the PEG 6000 will make the suppository more solid. Thus, the time taken for the suppository to melt should actually increases with the amount of PEG 6000 in the suppository.

            Based on the results we obtained, the longest time is used to melt the suppository that has the highest amount of PEG 6000, which is 9g. This does comply with the theory. However, the results deviate for the suppositories that contain 0 and 3g of PEG 6000 g. For these 2 suppositories, the average time needed decreases with the increasing amount of PEG 6000. This shows that the results we obtained is inappropriate.

            The deviation of the result from the story is majorly effected by the errors occur while conducting the experiment. Defect of suppository made reduction in mass and will reduce the time for suppository to dissolve. Error made during measuring and transferring the ingredient while making suppository may also alter the results. There is also a 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. Another causes may due to 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. Analyse it.

This experiment was used to determine the absorption rate of the suppository in human body. In this experiment, the dialysis bag represents human biological membrane while distilled water represents human blood plasma. This experiment is carried out in water bath at 37ºC, which represents human body temperature. Due to the concentration gradient, the high concentration of water molecules of distilled water will diffuse into the dialysis bag whereas the high concentration of particles in paracetamol suppository diffused out of dialysis bag into distilled water. The paracetamol suppository melted at 37 ºC.

The graph shows that the UV absorption is increasing with time. It indicated that the amount of paracetamol released into distilled water is increasing with time. The longer the time, the higher amount of paracetamol released to the distilled water. Theoretically, a sigmoid graph will be obtained in this experiment due to the constant drug release rate until reaches the equilibrium. However, the graph we obtained shows the inconstant release of paracetamol. This happened due to some errors in this experiment. One of the errors is the uneven stirring of distilled water before it is taken for the measuring of results. Besides that, the water bath may not maintain at 37 ºC. Next, the distribution of paracetamol in the suppository is not homogenous. This is due to the air bubble trapped inside the suppository during the preparation of suppositories. This leads to the alteration of the drug release rate. Lastly, the reading was not taken at exactly 5 minutes interval. All of these lead to the inaccuracy of the results.

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

           

           There are 4 parameters of an in vitro suppository drug release, which are temperature, contact area, release medium and membranes. Throughout the experiment, 37^oC is used for the experiments of drug release from the suppositories. Measurements of drug release at 37^oC may become an over estimation due to the differences in melting range of the suppositories.

            There is no apparatus to mimic the contact area between the suppository and the rectal mucosa. This is important in determining the rate of drug release of the suppository. As long as this is not developed, the results are not tailor-made for the real condition, inaccurate results may be produced.

Distilled water is considered as the release medium in this experiment. However, we should know that there is no ideal solution yet due to the problem of choosing a suitable volume and composition of the release medium that suits the condition in the rectal area.

            The “membrane” we used in this experiment is the dialysis bag. This may come with an enormous drawback as the release measured in the outer compartment is not equal to the actual release that is taking place in the inner compartment. The membrane may form a resistance to passing drug molecules. The actual release may be underestimated.

Based on the graph, there is a wide range of variation which do not correlates with the theoretical principle. Theoretically, suppositories that are prepared with the different combination of PEG 1000 and 6000 show different release rate of drug against the time that contribute to solubility and dissolution of drugs in the aqueous medium. Hence, the graph obtained for the four different formulations of suppositories should be increasing initially and then become constant gradually as all the drug is released into the water and diffuses out from the hydrophilic matrix with time. And, the suppository with the highest amount of PEG 6000 will show the slowest release rate due to the stronger hydrogen bonds formed with Paracetamol substances which hinders the release of Paracetamol. Decreasing the high molecular weight PEG (6000) concentration and increasing low molecular weight PEG (1000) concentration in the base resulted enhancing the in-vitro release of the drug and vice versa. Water solubility of the drug suppository increases as the molecular weights of PEG decrease due to the water absorbing properties of PEG. Thus, the highest rate of release is expected for suppository I due to the lowest proportion or amount of PEG 6000 in the formulation while formulation suppository IV with higher contents of PEG 6000 will give the slowest releasing rate of drug due to the strong hydrogen bond among molecules PEG 6000 with molecules Paracetamol. The UV absorption will increase with time until it reaches a plateau stage where the entire drug has been released.

However, from the graph obtained, suppository II shows the higher rate of drug release than suppository I which is deviates from the theory. In fact, the suppository II has higher concentration of PEG 6000 and lower concentration of PEG 1000 that should have lesser drug release rate than I. Suppository II shows the higher rate of drug release than suppository III as it has higher composition of PEG 1000 and lower amount of PEG 6000 that slow the release rate of drug. This obeys to the theory.

            Deviations or inaccuracy occurred in the experiment may be due to impurities, parallax error, and equipment used give inaccurate readings, uneven temperature of the water bath and others. Existence of impurities results from improper cleaning of the cuvette for assay. Cuvettes that are not properly dried before we insert a new sample for assay may affect the readings. Dialysis bag that is not tied well before inserting into water bath leads to the fluctuation readings. Besides, inaccuracy of readings may also caused by the obtained sample form unstirred solution in beaker before analysis.

            Therefore, several precautions should be taken during the experiment likewise ensuring the cuvette is dried completely before inserting into the absorption spectrophotometer. We should stir the solution containing sample in the beaker before taking the sample for analysis. Lastly, ensure that our beaker containing the sample is always maintained at even temperature in water bath. These precautions may cut down the deviations formed from errors in conducting experiments.

    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?

Ingredients that used in this experiment are Paracetamol, PEG 1000 and PEG 6000. The Paracetamol acts as the active ingredient in this suppository. It is the main substance in this formulation which contributing to the therapeutic effects. While PEG is Polyethylene Glycol which acts as suppository bases in this formulation. Polyethylene glycols are polymers of ethylene oxide and water prepared to various chain lengths, molecular weights, and physical states. They are available in a number of molecular weight ranges, the most commonly used being polyethylene glycol 300, 400, 600, 1,000, 1,500, 1,540, 3,350, 4,000, 6,000, and 8,000. PEG are water soluble or water miscible type of bases that commonly used as suppository bases in pharmaceutical industry. It is because the special characteristic of PEG that has low melting point that suitable to be in body temperature. Various active ingredients can be dissolved in PEGs and have a good bioavailability. They act as carrier bases, solubilisers and absorption improvers for the drugs. Suppository that used higher amount of PEG 6000 take a longer time to release the active ingredient due to the melting point is around 56˚C to 63˚C while the melting point of PEG 1000 is in 37˚C to 40˚C range which as body temperature range. However, for a better shelf life the combination of PEG 1000 and PEG 6000 is important to produce slightly higher melting point of suppository and not easily melt on the shelf.

 PEG 6000 has higer molecular weight compare to PEG 1000.Higher proportions of high molecular weight polymers produce preparations which release the drug slowly and are also brittle. Less brittle products which release the drug more readily can be prepared by mixing high polymers with medium and low polymers. The PEG 1000 give very soft masses while PEG 6000 will give more solid products. The use of different contents of PEG 1000 and PEG 6000 results in different effects on the physical characteristics of the suppository produced and this will subsequently affect the rate of drug released from the suppository. More hydrogen bonds are formed between the PEG 6000 molecules and drug molecules when the more PEG 6000 is used. This will result in the increase of the hardness of the suppository and also the difficulty of the drug released from the suppository. The production of whitish, very hard, less sticky and very rough suppository will be obtained. On the other hand, PEG 1000 produces whitish, very soft, most sticky, and very smooth suppository. Thus, suitable and appropriate combination ratio of PEG 1000 and PEG 6000 is important in the production of an optimum drug delivery with optimum bioavailability of drugs available to the body and also to avoid too hard or too soft suppository.

Conclusion：

The suppository composition will affect the physical property and the drug release rate from the suppository. The higher the amount of PEG 6000, the suppository will be harder. 

Reference:

1. TorsenHennig, Polyethylene glycols (PEGs) and the pharmaceutical industry, Fine,speciality and Performance Chemicals, June 2002