THE EFFECT OF DIFFERENT AMOUNT OF PEG ON THE PHYSICAL CHARACTERISTICS OF SUPPOSITORY

Introduction:

Suppositories are solid dosage forms of various sizes, appearance (shapes) and weights intended for administration commonly by rectal route, vaginal route or even urethral where they melt, soften or dissolve to exert their effect. Suppositories come in variety of sizes and shapes where they are capable of being easily inserted into the intended orifice without causing undue distention. Moreover, suppositories can be used for two main purposes. The first is to act locally as a protective around the tissue where it is inserted and on the other hand suppository can not only act simply as a vehicle or carrier of an active drug, that we want to be absorbed at site of action but it can also be distributed systematically to produce an effect throughout the entire body.

The suppository usually composed of a medicament incorporated (dissolved or suspended) in a suppository base, this medicament may be intended for retention within the cavity for localized drug effect or to be absorbed for the exertion of systemic effect. For example, rectal localized action such as relief of constipation, pain, itching and inflammation associated with hemorrhoid conditions. Suppositories are indicated for systemic action in pediatric patients and in patients who cannot take or tolerate oral medication due to variety of reasons e.g. to relief nausea, vomiting and pain. The drug must be spread in a suitable base of suppository. Ideal suppository bases should be easily formed by compression or molding; release any medicament readily; melt at body temperature or dissolve or disperse in body fluids; keep its shape when handled; compatible with the drugs, non-irritant and non-toxic.

Polyethylene glycol (PEG) polymers have received much attention as suppository bases in recent years because they possess many desirable properties. They are chemically stable, non-irritating, miscible with water and mucous secretions, and can be formulated, either by mold or compression, in a wide range of hardness and melting point. Moreover, they do not melt at body temperature, but dissolve to provide a prolonged release. Certain PEG polymers may be used singly as suppository bases but, more commonly, formulas call for compounds of two or more molecular weights mixed in various proportions as needed to yield a finished product of satisfactory hardness and dissolution time.

Objectives:

·        To calibrate suppository mould with PEG before preparing medicated suppositories.

·        To determine the effect of different compositions of PEG base on the physical characteristics of suppositories.

3.0 Materials and methodology:

3.1 Apparatus:

           

·        Water bath at 37oC	·        1 x Suppository mould set
·        Hotplate	·        1 x Spatula
·        4 x 50 mL beaker	·        4 x Weighing boats
·        1 x 5 mL pipette and pipette bulb	·        2 x Glass rod
·        1 x 5 mL measuring cylinder	·        Analytical balance

           

3.2 Materials:

·        Polyethylene glycol (PEG) 1000	·        Distilled water
·        Polyethylene glycol (PEG) 6000	·        Liquid paraffin
·        Paracetamol

3.3 Methodology

3.3.1 Calibration of Suppository Molds with PEG Base

For the calibration exercise, 10 g of following proportion PEG 1000 and PEG 6000 had been used.

Ingredients	Percentage	Weight Basis
PEG 1000	60%	6.00 g
PEG 6000	40%	4.00 g

To calibrate the mold with PEG suppository base:

1. A clean and dry mold is taken and the mold is not lubricated.

2. The PEG 1000 is melted on a steam bath or hot plate, then, the heat is reduced and mixed with other PEG.

3. The mixture is removed from the heat and is allowed to cool before pouring into the mold.

4. The cavities are overfilled in the mold and is left to solidify at room temperature.

5. The excess is carefully removed with a hot spatula; the suppositories were removed from the mold.

6. The suppositories are weighed and the total weight is recorded. The average suppository weight is calculated.

3.3.2 Preparation of paracetamol suppositories

1. Saturated stock solution of paracetamol is prepared by adding 10 g of paracetamol in 5 mL distilled water.

2. Paracetamol suppository is prepared using the following formulation:

                    

Suppository	PEG 1000 (g)	PEG 6000 (g)	Paracetamol stock solution (mL)	Total (g)
I	9	0	1	10
II	6	3	1	10
III	0	9	1	10

3. Each type of PEG is melted on the steam bath or hot plate, then, the heat is reduced and mixed with other PEG.

4. The mixture is removed from heat and is allowed to cool down before pouring into the mold.

5.  The cavities are overfilled in the mold and is left to solidify at room temperature.

6. The excess is carefully removed with a hot spatula; the suppositories were removed from the mold.

7. The shape, texture and colour of the suppositories are observed.

8. Each of the suppositories are put into separate beaker containing distilled water ( 10 mL and pre-warmed at 37 ^oC)  and the beaker is put into the water bath.

9. The time for the suppositories to melt is recorded.

Results:

Calibration of suppository molds with PEG base.

Mold
Total weight for 6 suppositories	6.457 g
Average weight for 1 suppository	1. 076g

Suppositories	I	II	III
Time taken to melt (min)	47.34	42.11	54.48
Shape	Bullet	Bullet	Bullet
Hardness	Low	Medium	High
Greasiness	High	Medium	Low
Color	Clear White	Clear White	Pale White

Discussion :

1. Describe the important of calibrating suppository mould before preparing medicated suppository

The calibration of suppository mould is required to be done as each individual mold is capable of holding a specific volume of material in each of its openings. For example, the weight of suppository made up of cocoa butter will differ from the weight of suppository prepared in the same mold with a polyethylene glycol base (PEG) due to the differences in the density of the base materials. Therefore, any addition of medicinal agents alters the density of the base and the weight of the resulting suppository will differ from the suppository that has been prepared with base material alone. This is the reason why a pharmacists calibrates the suppository mold with a common base; to ensure that the medicated suppository will contain proper amount of medicament.

2. Compare the physical appearance of suppositories that are formed and discuss.

The shape for all Paracetamol suppositories are bullet shape because they are made using the same mold. The higher the molecular weight, the more hydroxyl group, the higher its melting point. As a result, the melting point for suppository III, which has 9g of PEG 6000, is the longest and supposedly the melting point point for suppository I is the fastest but somehow our result deviate because suppository II melt faster.  This could be due to error while conducting this experiment.  The same relationship can be used to explain the hardness of the suppositories, the more amount of PEG 6000 the harder the suppository will be.. Suppository I is more greasy than the other suppositories because it contain 9g of PEG 1000. PEG 1000 is more hydrophobic than PEG 6000 so, the higher amount of PEG 1000, the more greasy the suppository will be.

3.. Plot a graph of time required to melt the suppository vs. the amount of PEG 6000 in the formulation. Compare and explain the results.

From the graph,it is known that suppositories that have higher amount of PEG 6000 melt less rapidly than others suppositories using lesser amount of PEG 6000.This can be attributed to the physical properties of the suppositories itself, suppositories having high amount of PEG 6000 exhibit increase hardness and brittle properties,which upon contact with water or aqueous solution,disintegrate more easily than those suppositories having lower amount of PEG 6000 and appear soft.

4.  Describe function(s) of each ingredients used in the suppository formulation.

            The ingredients used in the suppository formulation is PEG 1000, PEG 6000 and paracetamol. Paracetamol is the active ingredient in the suppository. Paracetamol is also known as acetaminophen. It has analgesic effect and antipyretic effect. It can help to relieve pain and fever. It is typically used for mild to moderate pain.

            Polyethylene glycols are polymers of ethylene oxide and water which has various chain lengths, molecular weights, and physical states. They are chemically stable, nonirritating, and miscible with water and mucous secretions and can be formulated, either by molding or compression, in a wide range of hardness and melting point. The higher the molecular weight of PEG, the harder the suppositories formed and the higher the melting point.. Certain polyethylene glycol polymers may be used singly as suppository bases but, more commonly, two or more PEG with different molecular weights are used to yield a finished product of satisfactory hardness and dissolution time.

Since PEG is a water miscible bases, the suppository will dissolve in body fluids and thus, need not to be formulated to melt at body temperature. Hence, it can be formulated with much higher melting points and thus may be safely stored at room temperature. Formulation with higher amount of PEG 6000 compare to PEG 1000 will take a longer time to melt completely and thus, has slower release rate of drug.

Conclusion:

As a conclusion, different composition in the suppository will affect the physical property and the rate of drug release from the suppository. Higher amount of PEG 6000, the more harder the suppository and the higher its melting point.

Content of ibuprofen (assay)

Title

Content of ibuprofen (assay)

Aim

To determine the content of ibuprofen

Introduction

Ibuprofen is a painkiller, which is available over-the-counter, without a prescription. It is one of a group of painkillers called non-steroidal anti-inflammatory drugs (NSAIDs), and can be used to ease mild to moderate pain such as toothache, migraines and period pain, to control a fever which is in high temperature, also known as pyrexia, to ease pain and inflammation caused by rheumatic diseases and musculoskeletal disorders and to ease pain and swelling caused by sprains and strains, such as sports injuries.

Ibuprofen should be avoided by people with certain health conditions, such as a current or recent stomach ulcer, or a history of bad reactions to NSAIDs. It should be used with caution by older people, and people with certain health conditions, including asthma or kidney or liver problems.

Ibuprofen is made by many different companies, under many different brand names and in a wide range of forms, including tablets or caplets, gels, sprays and liquids. The dosage prescribed usually for adult and child over 12 years, initially 300-400mg, 3-4 times daily. The dosage will increased if necessary to maximum 2.4 g daily. The maintenance dose of 0.6-1.2g daily may be adequate. The dosage given of Ibuprofen to children who had pain and fever are different in age range. Usually Ibuprofen is marketed which 200 mg ibuprofen in a tablet. In oral suspension the content of ibuprofen is 100mg/5ml.

Figure 1: Structure of ibuprofen

Apparatus

Weighing boat, electronic balance, spatula, conical flask, beaker, dropper, measuring cylinder, filter funnel, filter paper, glass rod, hair dryer, burette, titration burette clamps.

Materials

20 tablets of Ibuprofen, 50 ml chloroform, 100 ml ethanol, phenolphthalein, 0.1 M sodium hydroxide.

Procedure

1. 20 Ibuprofen Tablets are weighed and powdered previously selected at random.

2. Quantity of powder containing 0.5 g ibuprofen is extracted with 20 ml chloroform for 15 minutes and filtered through a sintered glass crucible (BS Porosity No. 1).

3. The residue is washed with 3 × 10 ml chloroform and the combined filtrate is evaporated gently just to dryness in a current of air. The residue is dissolved in 100 ml ethanol (96%) previously neutralized to phenolphthalein solution.

4. The solution is titrated with 0.1 M sodium hydroxide to end point with phenolphthalein solution as indicator. The content of ibuprofen is calculated as each ml of 0.1 M sodium hydroxide is equivalent to 0.02063 g of C13H18O2.

Result and calculations

Observation: The solution turns from colourless to pink in titration.

Materials	Weight (g)
Powder of Ibuprofen + weighing boat	11.1400
Weighing boat	3.2000
Powder of Ibuprofen	7.9400

Weight of powder of 20 tablet Ibuprofen: 7.9400 g

1 tablet contain 200 mg Ibuprofen

20 tablet contains 20 x 200 mg Ibuprofen = 4000 mg = 4 g Ibuprofen

4 g Ibuprofen contains 7.9400 g of tablet powder

0.5 g Ibuprofen contains:

 0.50g/4.00g= x/7.94g

x = 0.9925 g of powder contain 0.5 g Ibuprofen

Thus, 0.9925 g of tablet powder was weighed and dissolved with 20 ml chloroform.

NaOH + C13H18O2  C13H17ONa + H2O

Initial burette reading of 0.1 M NaOH = 30.0 ml

End point reading of 0.1 M NaOH = 50.1 ml

Volume of 0.1 M NaOH = 50.1 ml – 30 ml = 20.1 ml

No. of mole of NaOH used in titration =MV/1000

If 1 ml 0.1 M NaOH is equivalent 0.02063 g C13H18O2.

20.1 ml 0.1 M NaOH is equivalent to 0.02063 g x 20.1 ml = 0.4147 g C13H18O2.

Thus, the content of ibuprofen is 0.4147 g.

Discussion

Percentage of deviation = (experiment value-theoretical value)/ theoretical value x 100%

Theoretically, 0.9925 g of Ibuprofen tablet powder contains 0.5 g Ibuprofen

Percentage of deviation = (0.4147g-0.5g)/0.5g x 100% = 17.06%

     

      The percentage of deviation is not too large, which is 17.06%. This might be caused by some errors done during the experiment. Errors might be done during the powder of Ibuprofen tablets using mortar and pestle. Some powder might be displaced out of the mortar when too much force was applied when powdering the tablets which lead to decrease in mass of the total Ibuprofen powder which causes inaccurate results. Besides, error might be done when the process of filtration was not being conducted properly as filter paper of smaller size was used and the residue is not being filtrated completely before proceeding to the next step. Another error might occur when drying the filtrate. The filtrate might be over dried and the ibuprofen evaporated, causing the mass of ibuprofen decreased and leading to inaccurate results. Apart from this, error might be done during titration when the process was stopped and the reading of volume was obtained when the end-point was not being reached which leads to inaccurate volume of NaOH needed. Parallax errors might also occur throughout the experiment when the eye level was not perpendicular to the reading scale on the measuring cylinder while measuring the solution. Beside this, the Ibuprofen tablets used were expired, which might have reduced amount of Ibuprofen content.

To overcome the errors above, some precaution steps should be taken. Firstly, powdering of Ibuprofen tablets should be done carefully by applying force enough to powder the tablet but not causing the powder to spill out of the mortar. Besides, the filtration process should be carried out more properly by using filter paper of appropriate size and patiently wait until all residue being filtered. During drying of filtrate using a hot gun, drying should be stopped once the liquid being evaporated but not until the white residue which is the ibuprofen being evaporated. Apart from this, the titration should only be stopped when the end point which is when the solution turns pale pink, has reached. Parallax errors should be avoided by placing the eye level perpendicular to the reading scale on the measuring cylinder while measuring volumes of solutions. Besides, Ibuprofen tablets used must not be expired to obtain a more ideal results.

Conclusion

The percentage of deviation is 17.06% which means that the content of ibuprofen is 82.94% of the labeled content. Besides, the errors must be prevented to obtain more accurate results.

Reference

1. http://www.nhs.uk/Conditions/Painkillers-ibuprofen/Pages/Introduction.aspx

2. http://pubchem.ncbi.nlm.nih.gov/compound/ibuprofen